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Lamina Propria (lamina + propria)
Terms modified by Lamina Propria Selected AbstractsCollagen Fiber and Versican Distribution Within the Lamina Propria of Fetal Vocal Folds,THE LARYNGOSCOPE, Issue 2 2008Rogerio Borghi Buhler MD Abstract Objectives: To analyze the presence and distribution of collagen fibers and versican in human vocal fold lamina propria of fetal larynges. Study Design: Cross sectional analysis of cadaveric vocal folds of human fetuses. Methods: Seven fetal larynges obtained from 28- to 36-week-old fetuses were analyzed with the Picrosirius-polarization method, immunohistochemistry, and image analysis. Results: Collagen fibers within the lamina propria exhibited a monolaminar distribution pattern and spatial arrangement in "wicker basket." Versican distribution was larger in the superficial and intermediate layers when compared to the deep layer. Conclusion: Our findings suggest that collagen and versican distribution and arrangement within the lamina propria in the developing fetus are important for vocalization at birth. [source] Development and Maturation of the Pediatric Human Vocal Fold Lamina Propria,THE LARYNGOSCOPE, Issue 1 2005Christopher J. Hartnick MD Abstract Objective: To identify characteristic patterns of maturation of the human vocal fold lamina propria as it develops into a mature structure. Methods: Histologic evaluation of sectioned true vocal folds from 34 archived larynges ages 0 to 18 years using hematoxylin-eosin, trichrome, Alcian blue pH 2.5, Weigert reticular, and Miller's elastin stain. Location: Pathology department at a tertiary care children's hospital. Results: At birth and shortly thereafter, there exists a relative hypercellular monolayer of cells throughout the lamina propria. By 2 months of age, there are the first signs of differentiation into a bilaminar structure of distinct cellular population densities. Between 11 months and 5 years, two distinct patterns are seen: 1) this bilaminar structure and 2) a lamina propria where there exists a third more hypocellular region immediately adjacent to the vocalis muscle (this region is similar to the superficial hypocellular region found just deep to the surface epithelium). By 7 years of age, all of the specimens exhibit this transition between the middle and the deeper layers according to differential density of cell populations. A lamina propria structure defined by differential fiber composition (elastin and collagen fibers) is not present until 13 years of age and then is present throughout adolescence. Conclusions: Using the classic adult model of fiber composition and density to differentiate the layered structure of the lamina propria of the human vocal fold may not adequately allow for a thorough description of the process of maturation and development. Rather, distinct regions of cell density are seen as early as 2 months postpartum, and the model of cellular distribution may serve better to describe the lamina propria as it develops. Cell-signaling processes that shape the formation of the lamina propria appear to produce layered populations of differential cell density that in turn will later produce differential fiber compositions. Early development therefore can be followed by evaluating the maturation of these differing cell populations. Future studies are needed to quantify these cell distribution patterns, to study the cell signaling processes that trigger this maturation, and to correlate these findings with mechanical modeling. [source] Site-specific expression of CD11b and SIRP, (CD172a) on dendritic cells: implications for their migration patterns in the gut immune systemEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2005Diane Bimczok Abstract Dendritic cells (DC) in the intestinal tract play a major role in directing the mucosal immune system towards tolerance or immunity. We analyzed whether different mucosal DC subsets in pigs have specific functions, localizations, or migration patterns in vivo. Therefore, we collected physiologically migrating DC by pseudo-afferent cannulation of the intestinal duct in eight Göttingen minipigs. Lymph DC were phenotypically and functionally characterized and compared to DC found on histological sections of porcine small intestine and mesenteric lymph nodes (MLN). Four different DC subpopulations were detected. Lamina propria (LP) DC were mainly CD11b+ signal regulatory protein,, (SIRP,)+, DC in Peyer's patches were mainly CD11b,/SIRP,+ in subepithelial domes and CD11b,/SIRP,, in interfollicular regions, whereas MLN DC were largely CD11b+/SIRP,,. Of these four subsets, only the CD11b+/SIRP,+ DC and the CD11b+/SIRP,, DC were present in lymph. This suggests that DC migration to MLN largely originates from the LP. Lymph DC expressed high levels of MHC class,II and costimulatory molecules and had a low capacity for FITC-dextran uptake, indicating a mature phenotype. However, lymph DC did not induce PBMC proliferation in MLR, and migration was not significantly influenced by mucosal antigen application. [source] Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine-protective regulatory T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2009Yingzi Cong Abstract The gut is home to a large number of Treg, with both CD4+ CD25+ Treg and bacterial antigen-specific Tr1 cells present in normal mouse intestinal lamina propria. It has been shown recently that intestinal mucosal DC are able to induce Foxp3+ Treg through production of TGF-, plus retinoic acid (RA). However, the factors instructing DC toward this mucosal phenotype are currently unknown. Curcumin has been shown to possess a number of biologic activities including the inhibition of NF-,B signaling. We asked whether curcumin could modulate DC to be tolerogenic whose function could mimic mucosal DC. We report here that curcumin modulated BM-derived DC to express ALDH1a and IL-10. These curcumin-treated DC induced differentiation of naïve CD4+ T cells into Treg resembling Treg in the intestine, including both CD4+CD25+ Foxp3+ Treg and IL-10-producing Tr1 cells. Such Treg induction required IL-10, TGF-, and retinoic acid produced by curcumin-modulated DC. Cell contact as well as IL-10 and TGF-, production were involved in the function of such induced Treg. More importantly, these Treg inhibited antigen-specific T-cell activation in vitro and inhibited colitis due to antigen-specific pathogenic T cells in vivo. [source] Strategies for optimizing targeting and delivery of mucosal HIV vaccinesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2009Jeffrey D. Ahlers Abstract Effective frontline defenses against HIV-1 will require targeting vaccines to mucosal tissue in order to induce ,, CD8+ lymphocytes in mucosal effector sites (lamina propria and intraepithelial compartment) as well as antibody secreting plasma cells that can neutralize and limit free virus. A concerted second wave of assault against the virus will require the activation and recruitment of antigen specific memory CD4+ and CD8+ T cells in mesenteric lymph nodes and distal secondary lymphoid organs. New delivery strategies targeting the "right" DC subsets in combination with delivery of mucosal adjuvants and innate signals for activating DC will be essential for mucosal vaccines in order to circumvent the naturally tolerogenic environment and the induction of Tregs. Mucosal delivery of antigen in combination with inflammatory signals has been shown to empower systemic immunization by directing responses to mucosal sites for imprinting optimum mucosal memory. Here, we discuss novel vaccine strategies and adjuvants for optimizing mucosal delivery of HIV vaccines. [source] Intestinal double-positive CD4+CD8+ T,cells are highly activated memory cells with an increased capacity to produce cytokinesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2006Bapi Pahar Dr. Abstract Peripheral blood and intestinal CD4+CD8+ double-positive (DP) T,cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. Here we demonstrate that DP T,cells are abundant in the intestinal lamina propria of normal rhesus macaques (Macaca mulatta). Moreover, DP T,cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen stimulation compared to CD4+ single-positive T,cells. Intestinal DP T,cells are also highly activated and have higher expression of CCR5, which makes them preferred targets for simian immunodeficiency virus/HIV infection. Increased levels of CD69, CD25 and HLA-DR, and lower CD62L expression were found on intestinal DP T,cells populations compared to CD4+ single-positive T,cells. Collectively, these findings demonstrate that intestinal and peripheral blood DP T,cells are effector cells and may be important in regulating immune responses, which distinguishes them from the immature DP cells found in the thymus. Finally, these intestinal DP T,cells may be important target cells for HIV infection and replication due to their activation, memory phenotype and high expression of CCR5. [source] MHC class II-independent CD25+ CD4+ CD8,,,+ ,,, T cells attenuate CD4+ T cell-induced transfer colitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2004Tamara Krajina Abstract CD4+ ,,, T cell populations that develop in mice deficient in MHC class II (through ,knockout' of either the A,, or the A, chain of the I-Ab molecule) comprise a major ,single-positive' (SP) CD4+ CD8, subset (60,90%) and a minor ,double-positive' (DP) CD4+ CD8,,,+ subset (10,40%). Many DP T cells found in spleen, mesenteric lymph nodes (MLN) and colonic lamina propria (cLP) express CD25, CD103 and Foxp3. Adoptive transfer of SP but not DP T cells from A,,/, or A,,/, B6 mice into congenic RAG,/, hosts induces colitis. Transfer of SP T cells repopulates the host with only SP T cells; transfer of DP T cells repopulates the host with DP and SP T cells. Anti-CD25 antibody treatment of mice transplanted with DP T cells induces severe, lethal colitis; anti-CD25 antibody treatment of mice transplanted with SP T cells further aggravates the course of severe colitis. Hence, regulatory CD25+ T cells within (or developing from) the DP T cell population of MHC class II-deficient mice control the colitogenic potential of CD25, CD4+ T cells. [source] Contrasting effects of basic fibroblast growth factor and epidermal growth factor on mouse neonatal olfactory mucosa cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007Perrine Barraud Abstract Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) affect proliferation and survival of many cell types, but their role in the maintenance of olfactory mucosa cells remains unclear. In the neonatal mouse olfactory mucosa, cell proliferation mainly occurs in the neuroepithelium and, to a lesser extent, in the lamina propria. To establish whether bFGF and EGF affect proliferation and/or survival of these cells, we isolated olfactory mucosa cells from the neonatal mouse and cultured them as free-floating spheres under bFGF or EGF stimulation. Our data demonstrate that bFGF is a mitogen for the rapidly dividing cells (olfactory neuronal precursors and olfactory ensheathing cells), and also a survival factor for both slowly and rapidly dividing cells of the olfactory mucosa. In contrast, EGF appears to be primarily a survival factor for both the olfactory stem and precursor cells. [source] Effects of maxillary sinus floor elevation surgery on maxillary sinus physiologyEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 3 2003Nicolaas M. Timmenga In a prospective study, the effects of elevation surgery of the maxillary sinus floor on maxillary sinus physiology were assessed. Seventeen consecutive patients without preoperative anamnestic, clinical and radiological signs of maxillary sinusitis underwent sinus floor elevation surgery with iliac crest bone grafts. All patients were subjected to unilateral endoscopic examination of the maxillary sinus, taking of a biopsy specimen from the sinus floor mucosa, and collection of a sinus lavage-fluid aspirate. This triad of evaluations was performed immediately preceding the elevation procedure, and 3 months (at implant insertion) and 9 months (at uncovering of implants) postoperatively. All procedures were performed under general anesthesia. Preoperatively, three out of 17 patients showed pre-existing mucosal pathology endoscopically, while the 3- and 9-month results revealed the presence of mucosal pathology in four and two patients, respectively. The 3-month microbiological evaluation showed a significant increase in cultures with bacterial growth, while the 9-month culture results were comparable to the preoperative status of the maxillary sinus. Morphologically, neither fibrosis nor an altered inflammatory response or thickening of the epithelium and lamina propria was observed postoperatively. The number of goblet cells in the epithelial layer was increased. From this study it is concluded that the effect of maxillary sinus floor elevation surgery with autogenous bone grafts does not appear to have clinical consequences in patients without signs of pre-existing maxillary sinusitis. [source] Neutrophil influx during non-typhoidal salmonellosis: who is in the driver's seat?FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006Çagla Tükel Abstract A massive neutrophil influx in the intestine is the histopathological hallmark of Salmonella enterica serovar Typhimurium-induced enterocolitis in humans. Two major hypotheses on the mechanism leading to neutrophil infiltration in the intestinal mucosa have emerged. One hypothesis suggests that S. enterica serovar Typhimurium takes an active role in triggering this host response by injecting proteins, termed effectors, into the host cell cytosol which induce a proinflammatory gene expression profile in the intestinal epithelium. The second hypothesis suggests a more passive role for the pathogen by proposing that bacterial invasion stimulates the innate pathways of inflammation because the pathogen-associated molecular patterns of S. enterica serovar Typhimurium are recognized by pathogen recognition receptors on cells in the lamina propria. A review of the current literature reveals that, while pathogen recognition receptors are clearly involved in eliciting neutrophil influx during S. enterica serovar Typhimurium infection, a direct contribution of effectors in triggering proinflammatory host cell responses cannot currently be ruled out. [source] Natural Killer Cell Receptor+ T-Lymphocytes in Normal and Helicobacter pylori -Infected Human Gastric MucosaHELICOBACTER, Issue 6 2008Joan O'Keeffe Abstract Background:,Helicobacter pylori infection is associated with development of chronic inflammation and infiltration of immune cells into the gastric mucosa. As unconventional T-lymphocytes expressing natural killer cell receptors are considered to play central roles in the immune response against infection, a study investigating their frequencies in normal and H. pylori -infected gastric mucosa was undertaken. Materials and Methods:, Flow cytometry was used to quantify T-cells expressing the natural killer cell markers CD161, CD56, and CD94 in freshly isolated lymphocytes from the epithelial and lamina propria layers of gastric mucosa. Thirteen H. pylori -positive and 24 H. pylori -negative individuals were studied. Results:, CD94+ T-cells were the most abundant (up to 40%) natural killer receptor-positive T-cell population in epithelial and lamina propria layers of H. pylori -negative gastric mucosa. CD161+ T-cells accounted for about one-third of all T-cells in both compartments, but the lowest proportion were of CD56+ T-cells. Compared with H. pylori -negative mucosa, in H. pylori -infected mucosa the numbers of CD161+ T-cells were significantly greater (p = .04) in the epithelium, whereas the numbers of CD56+ T-cells were lower (p = .01) in the lamina propria. A minor population (< 2%) of T-cells in both mucosal layers of H. pylori -negative subjects were natural killer T-cells, and whose proportions were not significantly different (p > .05) to those in H. pylori -infected individuals. Conclusions:, The predominance, heterogeneity, and distribution of natural killer cell receptor-positive T-cells at different locations within the gastric mucosa reflects a potential functional role during H. pylori infection and warrants further investigation. [source] Clinicopathological characteristics of primary gastric T-cell lymphomaHISTOPATHOLOGY, Issue 6 2009Kenichiro Kawamoto Aims:, To investigate the clinicopathological characteristics of 20 primary gastric T-cell lymphoma (GTCL) cases without human T-lymphotropic virus type I infection in Japan, a non-endemic area for coeliac disease. Methods and results:, Fifteen cases had no history of persistent diarrhoea or severe hypoproteinaemia. Histologically, 13 cases (65%) consisted of large cell lymphoma and seven (35%) were of medium-sized cells. Intraepithelial lymphoma cell invasion was found in three cases (15%). Two of 10 surgical cases (20%) showed intramucosal tumour cell spreading with enteropathy-like features. Helicobacter pylori CagA gene was detected in three of 10 cases (30%). The lymphoma cells of all 20 cases were positive for CD3 and/or TCR,F1 and negative for CD56. CD4, and CD8, lymphoma was found in 11 cases (55%), CD4+ lymphoma in seven (35%) and CD8+ lymphoma in two (10%). CD30+, CD5+ and CD25+ lymphomas were detected in nine (45%), 10 (50%) and 11 (55%) cases, respectively. Five-year survival of the 16 available cases was 54%. Early clinical stage and medium-sized cell lymphoma were significantly (P < 0.05) better prognostic factors. Conclusions:, Patients with GTCL exhibit distinct clinicopathological findings and prognoses from those with enteropathy-associated T-cell lymphomas. GTCL may be mainly derived from lamina propria and parafollicular T cells. [source] Curriculum vitae of intestinal intraepithelial T cells: their developmental and behavioral characteristicsIMMUNOLOGICAL REVIEWS, Issue 1 2007Hiromichi Ishikawa Summary:, The alimentary tract has an epithelial layer, consisting mainly of intestinal epithelial cells (IECs), that is exposed to the exterior world through the intestinal lumen. The IEC layer contains many intestinal intraepithelial T cells (IELs), and the total number of IELs constitutes the largest population in the peripheral T-cell pool. Virtually all ,,-IELs and many ,,-IELs in the mouse small intestine are known to express CD8,, homodimers. A wide range of evidence that supports extrathymic development of these CD8,,+ IELs has been collected. In addition, while several studies identified cells with precursor T-cell phenotypes within the gut epithelium, how these precursors, which are dispersed along the length of the intestine, develop into ,,-IELs and/or ,,-IELs has not been clarified. The identification of lymphoid cell aggregations named ,cryptopatches' (CPs) in the intestinal crypt lamina propria of mice as sites rich in T-cell precursors in 1996 by our research group, however, provided evidence for a central site, whereby precursor IELs could give rise to T-cell receptor-bearing IELs. In this review, we discuss the development of IELs in the intestinal mucosa and examine the possibility that CPs serve as a production site of extrathymic IELs. [source] Lymphoid microenvironment in the gut for immunoglobulin A and inflammationIMMUNOLOGICAL REVIEWS, Issue 1 2003Robert Chin Summary:, Signaling through lymphotoxin , receptor (LT,R) initiates the unfolding of a host of developmental programs ranging from the organogenesis of lymph nodes and Peyer's patches (PPs) to the coordination of splenic microarchitecture. While investigating an alternative pathway to immunoglobulin A (IgA) production, it was uncovered that LT,R signaling in the lamina propria (LP) stroma orchestrates the coordinated expression of key chemokines and adhesion molecules, creation of a cytokine milieu, and stroma development that facilitates robust IgA production independent of secondary lymphoid structures. Simultaneously, this same infrastructure can be commandeered by autoreactive T cells to organize both the acute destruction of the intestinal mucosa and chronic intestinal inflammation via the ligands for LT,R. The ability to modulate LT,R signaling may alternatively permit the suppression of autoimmune responses and augmentation of gut defenses. [source] Human mid-gestation amniotic fluid contains interleukin-16 bioactivityIMMUNOLOGY, Issue 4 2009Catherine A. Thornton Summary CD4-positive cells are detectable in the human fetal gastrointestinal tract from 11 weeks of gestation. Interleukin-16 (IL-16) is a chemoattractant for CD4+ cells and, via fetal swallowing of amniotic fluid, could mediate the influx of CD4+ cells into the fetal gut. We have shown that IL-16 was detectable in human amniotic fluid at 16,18 weeks of gestation (mid-pregnancy) but was not detectable at term (late pregnancy; > 37 weeks of gestation). Similarly, mid-pregnancy, but not late pregnancy, amniotic fluid contained chemotactic activity for CD4+ T cells, this activity was reduced by 58% in the presence of a neutralizing anti-IL-16 antibody. The levels of IL-16 in fetal plasma at 16,24 weeks of gestation were very high, and decreased significantly by 25,36 weeks but at > 37 weeks remained significantly higher than adult levels. IL-16 transcripts were detectable in whole tissue extracts of fetal gut, skin and placenta but not in amniocytes, and IL-16 immunoreactivity was detectable in cells within the lamina propria of the fetal gut and within the skin, where it was associated with the basement membrane. Neither IL-16 levels nor chemotactic activity for CD4+ T cells in mid-pregnancy amniotic fluid was related to atopic outcomes at 1 year of age. IL-16 might have an important role in the early development of the human immune system and/or in regulating fetal and maternal immunological responsiveness during pregnancy. [source] CXCL12 Is a constitutive and inflammatory chemokine in the intestinal immune systemINFLAMMATORY BOWEL DISEASES, Issue 4 2010Iris Dotan MD Abstract Background: Inflammatory bowel disease (IBD) is characterized by increased lymphocytic infiltrate to the lamina propria (LP) and upregulation of inflammatory chemokines and receptors. CXCL12 is a constitutive chemokine involved in lung, brain, and joint inflammation. We hypothesized that CXCL12 and its receptor, CXCR4, would have a constitutive and inflammatory role in the gut. Methods: Intestinal epithelial cells (IECs) and T lymphocytes were isolated from intestinal mucosa of IBD and control patients undergoing bowel resection. Autologous T cells were isolated from peripheral blood (PB). CXCL12 and CXCR4 expression by IECs was assessed by polymerase chain reaction and immunohistochemistry, lymphocyte phenotype by flow cytometry, and migration by Transwells. Results: IECs expressed CXCL12 and expression was increased and more diffuse in IBD compared to normal crypts (ulcerative colitis [UC] > Crohn's disease [CD], inflamed > noninflamed). CXCR4 was expressed by IECs, LP T cells (LPTs), and PB T cells (PBTs), and CXCR4+ cells were increased in IBD LP in situ. PBTs and LPTs from all patients had a high and comparable migration toward CXCL12 (P < 0.0001 and P < 0.05 vs. medium, respectively). Migration toward IBD-IEC-derived supernatant was significantly higher compared to normal. Antibodies against CXCR4 and CXCL12 blocked migration. Conclusions: CXCL12 is expressed by normal IECs and upregulated and differentially distributed in IBD IECs. CXCR4 is expressed by IECs and LPTs, and CXCR4+ cells are significantly increased in IBD LP. CXCL12 is chemotactic for both PBTs and LPTs. Thus, CXCL12 and CXCR4 have a constitutive and inflammatory role in the intestinal mucosa and their selective therapeutic manipulation may be considered in IBD management. (Inflamm Bowel Dis 2009;) [source] Quantitive cytokine mRNA expression profiles in the colonic mucosa of patients with steroid naïve ulcerative colitis during active and quiescent diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2009Reikei Matsuda MD Abstract Background: Cytokines have validated roles in the immunopathogenesis of inflammatory bowel disease (IBD). This study was to investigate the expressions of tumor necrosis factor (TNF)-,, interleukin (IL)-6, IL-8, and IL-10 mRNAs in the colonic mucosa of patients with ulcerative colitis (UC) during active and quiescent UC. Methods: At colonoscopy, biopsies were taken from inflamed and non-inflamed mucosa of patients with steroid-naive UC (n = 15), non-IBD inflammatory colitis controls (ICC, n = 6), and non-colitis controls (NCC, n = 14). The presence of extensive mononuclear cells and neutrophils infiltrate in the lamina propria, cryptitis, and epithelial damage defined an inflammatory lesion in the mucosa. Quantitative cytokine mRNA expressions in biopsies were measured by real-time polymerase chain reaction (PCR). Results: Of 15 UC patients, 3 remitted with 5-aminosalicylate and 11 received granulocytapheresis; of these, 10 remitted. At baseline, IL-6, IL-8, TNF-,, and IL-10 mRNAs were high in inflamed mucosa compared with NCC (P < 0.01). In active UC, IL-6, IL-8 and IL-10 mRNAs were high compared with non-inflamed mucosa (P = 0.03, P = 0.03, P < 0.05, respectively). Both TNF-, mRNA (P = 0.03) and IL-6 mRNA (P = 0.04) were higher in UC compared with ICC. Even in non-inflamed mucosa, IL-8 and TNF-, mRNA expressions were high compared with NCC. Both IL-6 and IL-8 mRNAs decreased to normal levels after granulocytapheresis. Conclusions: During active UC, all 4 cytokine mRNA levels were high; only IL-6 and IL-8 mRNAs decreased to normal levels during remission. IL-8 mRNA was high even at sites of endoscopically quiescent UC during active disease. Steroid naïve patients respond well to granulocytapheresis. (Inflamm Bowel Dis 2008) [source] IL-23/IL-17 immunity as a hallmark of Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 9 2008Veera Hölttä MD Abstract Background: We studied the balance between ileal T-effector cells versus T-regulatory cells in active and inactive Crohn's disease (CD). Methods: We compared effector and regulatory T-cell-related markers such as interleukin (IL),17, interferon (IFN)-,, IL-4, and Foxp3 transforming growth factor (TGF),, CTLA-4 and markers for innate immune activation such as IL-6, IL-10, IL-18, IL-23, tumor necrosis factor (TNF),,, and IL-12p70, studied with immunohistochemistry and RT-PCR in ileal biopsies from patients with active or inactive CD and from control subjects. IL-17 in fecal samples was detected by ELISA. The effect of IL-17 on IL-8 and TNF-, mRNA expression in epithelial cell line Caco-2 was studied. Results: The numbers of IL-4-, IL-17-, and IL-23(p19)-positive cells in the lamina propria were higher in patients with CD, both active and inactive, than in the controls. mRNA expression of IL-17A, IL-6, and Foxp3 was increased in the biopsies both from patients with active disease and those in remission, whereas mRNA expression of IL-23 was increased only in active disease. Fecal IL-17 concentration was increased in patients with active disease. IL-17 enhanced the IL-8 and TNF-, response of the epithelial cell line to lipopolysaccharide (LPS) in vitro. Conclusions: Our findings suggest that activation of the IL-23/IL-17 axis is fundamentally connected to the etiology of CD and may represent the basis for the relapsing nature of the disease by increasing the sensitivity of epithelium to microbial LPS. (Inflamm Bowel Dis 2008) [source] Expression and functional characterization of FOXP3+CD4+ regulatory T cells in ulcerative colitis,INFLAMMATORY BOWEL DISEASES, Issue 2 2007Qi T. Yu BS Abstract Background: CD4+CD25+ regulatory T cells (TR) can prevent or treat experimental murine colitis but little is known about their potential role in human inflammatory bowel disease (IBD). FOXP3 is a transcription factor that plays a critical role in the development and function of CD4+CD25+ TR. The aim of this study was to examine the presence and functional characteristics of TR cells in colonic lymphoid tissues in patients with ulcerative colitis (UC). Methods: FOXP3 expression was assessed by flow cytometry, immunohistochemistry, and reverse-transcriptase polymerase chain reaction (RT-PCR). Functional characterization of CD4+CD25+ cells was analyzed by suppression of proliferation and secretion of cytokines by cocultured effector CD4+CD25, T cells. Results: FOXP3+CD4+ T cells are increased in the lamina propria (LP) of inflamed and noninflamed areas of UC colon compared to normal colon. CD4+CD25+ T cells in UC mesenteric lymph nodes (MLN) express FOXP3 mRNA and protein and suppress the proliferation of autologous MLN CD4+CD25, T cells. The suppressor activity of MLN CD4+CD25+ T cells is cell contact-dependent but cytokine-independent. In addition, CD4+CD25+ T cells potently suppress the production of both Th1 (IFN-,, IL-2) and Th2 (IL-5, IL-13) cytokines by cocultured CD4+CD25, T cells. FOXP3+ cells localized in the T-cell-rich areas of MLN and occasionally present in the follicles. Conclusions: There is an expansion of FOXP3+CD4+ T cells in mucosal lymphoid tissues in UC. CD4+CD25+ isolated from UC MLN express FOXP3 and display features of TR cells in spite of active mucosal inflammation. These data suggest that their suppressor activity may be abrogated in vivo or they are unable to counterbalance the chronic mucosal inflammation in UC. (Inflamm Bowel Dis 2007) [source] The proportion of CD40+ mucosal macrophages is increased in inflammatory bowel disease whereas CD40 ligand (CD154)+ T cells are relatively decreased, suggesting differential modulation of these costimulatory molecules in human gut lamina propriaINFLAMMATORY BOWEL DISEASES, Issue 11 2006Dr. Hege S. Carlsen MD Abstract Background: Signal transduction through binding of CD40 on antigen-presenting cells and CD40 ligand (CD154) on T cells appears to be crucial for mutual cellular activation. Antibodies aimed at blocking the CD40,CD154 costimulatory pathway dampen the severity of experimental colitis. To elucidate the microanatomical basis for signaling through this costimulatory pathway in human inflammatory bowel disease, we studied in situ the cellular distribution of these 2 molecules on lamina propria macrophages and T cells, respectively. Methods: Colonic specimens from 8 patients with ulcerative colitis and 8 with Crohn's disease, 8 small bowel specimens of Crohn's disease, and histologically normal control samples (6 from colon and 6 from small bowel) were included. Multicolor immunofluorescence in situ staining was performed to determine the percentage of subepithelial macrophages expressing CD40 and that of lamina propria T cells expressing CD154 while avoiding cells in lymphoid aggregates. Results: The proportion of subepithelial CD40highCD68+ macrophages was significantly increased in normal colon compared with normal small bowel and showed further elevation in both colon and small bowel afflicted with inflammatory bowel disease. In addition, on a per-CD68+ -cell basis, CD40 expression was significantly increased in severely inflamed compared with moderately inflamed colonic specimens. Conversely, the proportion of CD154+ T cells was similar in colon and small bowel, and interestingly, it was significantly reduced in colonic inflammatory bowel disease. Conclusions: Our findings suggested that modulation of CD40 expression by subepithelial macrophages and CD154 by lamina propria T cells is inversely modulated in the human gut. [source] Therapeutic effects of a new lymphocyte homing reagent FTY720 in interleukin-10 gene-deficient mice with colitisINFLAMMATORY BOWEL DISEASES, Issue 3 2004Tsunekazu Mizushima MD Abstract Background: FTY720 is a novel reagent that possesses potent immunosuppressive activity. The immunosuppression induced by FTY720 is mediated by completely different mechanisms from those of conventional immunosuppressants, that is, by altering the tissue distribution of lymphocytes rather than inhibiting activation. In this study, we examined the efficacy of FTY720 in the treatment of chronic colitis in an interleukin-10 gene-deficient (IL-10,/,) mouse model. Methods: FTY720 was administered orally for 4 weeks to IL-10,/,mice with clinical signs of colitis. The gross and histologic appearance of the colon and the numbers, phenotype, cytokine production, and apoptosis of lymphocytes were compared with those characteristics in a control group. Results: Single-dose administration of FTY720 resulted in the sequestration of circulating lymphocytes within the secondary lymphoid tissues. Four-week administration resulted in a significant reduction of the CD4+ T lymphocytes subpopulation in the colonic lamina propria and IFN-, production of the colonic lymphocytes, accompanied by a significant decrease in the severity of colitis. Conclusions: Treatment of established colitis in IL-10,/, mice with FTY720 ameliorated the colitis, probably as a result of decreasing the number of lymphocytes in the colonic mucosa and an associated reduction in IFN-, production. [source] Chemokine receptor CXCR3 expression in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2001Yu-Hong Yuan Abstract CD4+ T lymphocytes in the lamina propria (LP) of the gut play a central role in the immune response in inflammatory bowel disease (IBD). CXCR3 is a chemokine receptor expressed on activated T lymphocytes, and a key component for the recruitment of T helper (Th1) effector cells to the site of inflammation. To determine if CXCR3 is involved in localization of T cells to the gut in IBD patients, we investigated the expression of CXCR3 on CD4+ T lymphocytes in the LP and in the submucosa of resection specimens from 51 IBD patients and 15 control patients. Positive cells were microscopically scored using a semiquantitative analysis on a five-point scale. We found that CD4+ T cells, CXCR3+ cells, and CD4+CXCR3+ T cells in the LP were slightly increased in both IBD groups compared with control non-IBD specimens. In addition, CD4+ and CXCR3+ cells in the submucosa were significant increased in the CD group compared with the control group. CD4+ and CXCR3+ expression was not statistically different between CD and UC. Flow cytometry was used to analyze the percentage of CXCR3+ cells within the CD4+ T-cell population isolated from biopsy specimens and peripheral blood from IBD patients and control patients. There was no difference in the percentage of CD4+CXCR3+ cells between the different groups in the gut as well as in the circulation. These results suggest that CD4+CXCR3+ T cells migrate to the normal and inflamed intestinal mucosa, indicating a role in maintaining normal gut homeostasis. The selective expression of CXCR3+ cells in the submucosa of CD patients might also indicate that these cells play a role in inflammation. [source] Expression of plasminogen activator inhibitor-1, urokinase receptor and laminin ,-2 chain is an early coordinated event in incipient oral squamous cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Pia Lindberg Abstract Cancer cell invasion is facilitated by extracellular matrix degrading proteases such as plasmin. We have studied the expression of plasminogen activator inhibitor-1 (PAI-1) and urokinase receptor (uPAR) together with the ,2-chain of laminin-5 (lam-,2) by immunohistochemistry in 20 cases with incipient oral squamous cell carcinoma (SCC). PAI-1-positive neoplastic cells located at the tip of the putative invasive front of grade 1 (incipient) carcinoma were seen in 16 of the 20 cases (75%), whereas adjacent normal and dysplastic epithelium was PAI-1-negative. Clusters of putative invasive neoplastic cells located in the lamina propria were PAI-1-positive in areas with grade 2 incipient carcinoma as were invasive cancer cells in areas of grade 3,4 invasive carcinoma. uPAR immunoreactivity was strongly expressed in numerous stromal cells in the carcinoma area in all 20 lesions, while a few uPAR-positive stromal cells were found in areas with normal and dysplastic epithelium. uPAR-positive neoplastic cell islands located at the front of the lesions were seen in 15 of the 20 cases. The expression pattern of lam-,2 was very similar to that of PAI-1; however, lam-,2-positive neoplastic cells were only detected in 11 of the 20 cases (55%) in areas of grade 1 incipient carcinoma. Direct comparison of the 3 components revealed colocalization in neoplastic cell islands in both incipient and invasive SCC. Our results suggest that PAI-1 is a novel potential marker of initial invasion in oral SCC, and that the coordinated expression of PAI-1 with uPAR and lam-,2 sustain the features of the early invasive cancer cells. © 2006 Wiley-Liss, Inc. [source] Osteopontin as two-sided mediator of intestinal inflammationJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6 2009Katja Heilmann Abstract Osteopontin (OPN) is characterized as a major amplifier of Th1-immune responses. However, its role in intestinal inflammation is currently unknown. We found considerably raised OPN levels in blood of wild-type (WT) mice with dextran sodium sulfate (DSS)-induced colitis. To identify the role of this mediator in intestinal inflammation, we analysed experimental colitis in OPN-deficient (OPN,/,) mice. In the acute phase of colitis these mice showed more extensive colonic ulcerations and mucosal destruction than WT mice, which was abrogated by application of soluble OPN. Within the OPN,/, mice, infiltrating macrophages were not activated and showed impaired phagocytosis. Reduced mRNA expression of interleukin (IL)-1 , and matrix metalloproteinases was found in acute colitis of OPN,/, mice. This was associated with decreased blood levels of IL-22, a Th17 cytokine that may mediate epithelial regeneration. However, OPN,/, mice showed increased serum levels of tumour necrosis factor (TNF)-,, which could be due to systemically present lipopolysaccharide translocated to the gut. In contrast to acute colitis, during chronic DSS-colitis, which is driven by a Th1 response of the lamina propria infiltrates, OPN,/, mice were protected from mucosal inflammation and demonstrated lower serum levels of IL-12 than WT mice. Furthermore, neutralization of OPN in WT mice abrogated colitis. Lastly, we demonstrate that in patients with active Crohn's disease OPN serum concentration correlated significantly with disease activity. Taken together, we postulate a dual function of OPN in intestinal inflammation: During acute inflammation OPN seems to activate innate immunity, reduces tissue damage and initiates mucosal repair whereas during chronic inflammation it promotes the Th1 response and strengthens inflammation. [source] Response to soy: T-cell-like reactivity in the intestine of Atlantic salmon, Salmo salar L.JOURNAL OF FISH DISEASES, Issue 1 2007A M Bakke-McKellep Abstract T-cell-mediated hypersensitivity could be central in soybean meal (SBM)-induced intestinal changes in salmon. However, tools for immunohistochemical detection of T cells have been lacking in teleosts, including Atlantic salmon. Application of a specific histochemical protocol allowed demonstration of T-cell-like reactivities in formalin-fixed, paraffin-embedded tissues using an antibody reacting to a conserved region of human CD3, (Dako A0452). Characteristic staining was observed in cells of the thymus as well as distal intestine, skin, gills and spleen. These cells were negative for immunoglobulin M (IgM). Intestinal intraepithelial leucocytes were CD3, positive. During the SBM-induced enteropathy, the mixed inflammatory infiltrate in the lamina propria of the distal intestine included many lymphocytes with a T-cell-like reactivity. Real-time polymerase chain reaction revealed significantly increased expression of a complex polypeptide (CD3pp), CD4 and CD8, (P < 0.05) in the distal intestine of SBM-fed fish compared to fish meal-fed reference fish. Increased reactivity for extracellular IgM in the lamina propria and a positive material between the epithelial cells at the tips of the folds was observed, possibly due to leakage of IgM through an abrogated epithelial barrier. In conclusion, a T-cell-like response appears to be involved in this example of a food-sensitive enteropathy. [source] The production and characterization of monoclonal antibodies against Photobacterium damselae ssp. piscicida and initial observations using immunohistochemistryJOURNAL OF FISH DISEASES, Issue 2 2001T S Jung Five monoclonal antibodies (MAbs: F2B1, 1E4, 13B10, 4D4 and F3G12) were produced against lysed Photobacterium damselae ssp. piscicida (Ph. d. ssp. piscicida). The MAbs recognized three antigens of differing molecular weight on the Western blot of Ph. d. ssp. piscicida. They also cross-reacted with five different species of Vibrio. An enzyme linked immunosorbent assay (ELISA) with MAbs, F3G12 and 4D4 demonstrated differences between Ph. d. ssp. piscicida and three Ph. d. ssp. damselae type strains, indicating differences in the surface antigenicity between these two groups of bacteria. Antigen retrieval in conjunction with immunohistochemistry (IHC) using MAb 13B10, revealed colonies of bacteria in the kidney, spleen and liver of sea bass, Dicentrarchus labrax, infected with pasteurellosis. A number of positive colonies were observed around the mucosal layers of the intestinal tissue, especially within the lamina propria. In addition, a number of bacterial colonies were associated with red blood cells and blood vessels of the organs examined. [source] Changes in immune and enzyme histochemical phenotypes of cells in the intestinal mucosa of Atlantic salmon, Salmo salar L., with soybean meal-induced enteritisJOURNAL OF FISH DISEASES, Issue 2 2000A M Bakke-McKellep Extracted soybean meal (SBM) in the diet for Atlantic salmon, Salmo salar L., causes an inflammatory response in the distal intestine. The morphological changes of the epithelial cells and a characterization of the inflammatory cell infiltrate of the distal intestinal mucosa were studied using a panel of enzyme and immunohistochemical markers. The salmon (average body weight 927 g) used in the study were fed either a fishmeal-based diet (control diet) or a diet in which 30% of the fishmeal protein was replaced with SBM protein (SBM diet). In salmon fed SBM, there were markedly reduced enzyme reactivities in the distal intestinal epithelial cells, both in the brush border [5,-nucleotidase (5,N), Mg2+-ATPase, alkaline phosphatase (ALP) and leucine aminopeptidase (LAP)] and in the intracellular structures [alkaline and acid phosphatase, non-specific esterase (NSE) and alanine aminopeptidase (AAP)]. There appeared to be an increased presence of cells of monocytic lineage, including macrophages, as well as neutrophilic granulocytes and immunoglobulin (Ig) M in the lamina propria of the SBM-fed fish. The mid intestine showed little response to the diet. The results suggest that toxic/antigenic component(s) of SBM affect the differentiation of the distal intestinal epithelial cells and may help explain the reduced nutrient digestibilities previously reported in salmonids fed extracted SBM. [source] Expression of SLURP-1, an endogenous ,7 nicotinic acetylcholine receptor allosteric ligand, in murine bronchial epithelial cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 12 2009Kazuhide Horiguchi Abstract Mammalian secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) is a positive allosteric ligand for ,7 nicotinic acetylcholine (ACh) receptors (,7 nAChRs) that potentiates responses to ACh and elicits proapoptotic activity in human keratinocytes. Mutations in the gene encoding SLURP-1 have been detected in patients with Mal de Meleda, a rare autosomal recessive skin disorder characterized by transgressive palmoplantar keratoderma. On the basis of these findings, SLURP-1 is postulated to be involved in regulating tumor necrosis factor-, (TNF-,) release from keratinocytes and macrophages via ,7 nAChR-mediated pathways. In the present study, we assessed SLURP-1 expression in lung tissue from C57BL/6J mice to investigate the functions of SLURP-1 in pulmonary physiology and pathology. Immunohistochemical and in situ hybridization analyses revealed expression of SLURP-1 protein and mRNA, respectively, exclusively in ciliated bronchial epithelial cells. This was supported by Western blotting showing the presence of the 9.5-kDa SLURP-1 protein in whole-lung tissue and trachea. In addition, high-affinity choline transporter (CHT1) was detected in apical regions of bronchial epithelial cells and in neurons located in the lamina propria of the bronchus, suggesting that bronchial epithelial cells are able to synthesize both SLURP-1 and ACh. We also observed direct contact between F4/80-positive macrophages and bronchial epithelial cells and the presence of invading macrophages in close proximity to CHT1-positive nerve elements. Collectively, these results suggest that SLURP-1 contributes to the maintenance of bronchial epithelial cell homeostasis and to the regulation of TNF-, release from macrophages in bronchial tissue. © 2009 Wiley-Liss, Inc. [source] A possible CD1a Langerhans cell,mast cell interaction in chronic hyperplastic candidosisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 6 2007Ahmed Ali Aims:, T lymphocyte,antigen-presenting cell (APC) interaction plays a central role in T lymphocyte activation and APC maturation. We therefore studied the CD1a-positive Langerhans cells with respect to receptor activator of nuclear factor kappa B ligand (RANKL)-positive cells in chronic hyperplastic candidosis (CHC). Materials and methods:, Tissue sections of CHC were compared with leukoplakia and healthy oral mucosa using RANKL and CD1a monoclonal antibodies in an avidin,biotin peroxidase complex protocol. Two different antigen-retrieval protocols, pepsin preincubation and Tris,EDTA heat treatment, were used. Results:, CD1a-positive Langerhans cells were in healthy and leukoplakia epithelium found in the middle layer, but in CHC in all layers of the epithelium, at the basement membrane and as mononuclear round cells in the lamina propria. Use of pepsin digestion enabled studies of mast cells and their activation in the form of degranulation of RANKL. Conclusions:, The numerical, morphological and topographical versatility of the CD1a-positive Langerhans cells in CHC can be clarified by dendritic cell (DC) recruitment into the epithelium. RANK-positive and RANKL-sensitive DCs have ample opportunity to interact with local T lymphocytes. Use of an optimized antigen-retrieval protocol enabled demonstration of an active engagement (degranulation) of mast cells, which represent a rapidly available source of soluble RANKL. [source] Th1 cytokines in oral lichen planusJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 2 2003Ambereen Khan Abstract Background:, Cell-mediated immune responses in oral lichen planus (OLP) may be regulated by cytokines and their receptors. Methods:,In situ cytokine expression and in vitro cytokine secretion in OLP were determined by immunohistochemistry and ELISA. Results:, The majority of subepithelial and intraepithelial mononuclear cells in OLP were CD8+. In some cases, intraepithelial CD8+ cells were adjacent to degenerating keratinocytes. CD4+ cells were observed mainly in the deep lamina propria with occasional CD4+ cells close to basal keratinocytes. Mononuclear cells expressed IFN-, in the superficial lamina propria and TNF-, adjacent to basal keratinocytes. Basal keratinocytes expressed TNF-, as a continuous band. TNF R1 was expressed by mononuclear cells and basal and suprabasal keratinocytes. There was variable expression of TGF-,1 in the subepithelial infiltrate while all intraepithelial mononuclear cells were TGF-,1,. Keratinocytes in OLP stained weakly for TGF-,1. Unstimulated OLP lesional T cells secreted IFN-,in vitro. TNF-, stimulation down-regulated IFN-, secretion and up-regulated TNF-, secretion. IL-4, IL-10 and TGF-,1 secretion were not detected. Conclusions:, These data suggest the development of a T helper 1 immune response that may promote CD8+ cytotoxic T-cell activity in OLP. [source] | |||||||||||||||||||||||||||||||||||||