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FOXP3 mRNA (foxp3 + mrna)
Terms modified by FOXP3 mRNA Selected AbstractsHuman natural Treg microRNA signature: Role of microRNA-31 and microRNA-21 in FOXP3 expressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2009Redouane Rouas Abstract Treg are the main mediators of dominant tolerance. Their mechanisms of action and applications are subjects of considerable debate currently. However, a human microRNA (miR) Treg signature has not been described yet. We investigated human natural Treg and identified a signature composed of five miR (21, 31, 125a, 181c and 374). Among those, two were considerably under-expressed (miR-31 and miR-125a). We identified a functional target sequence for miR-31 in the 3, untranslated region (3, UTR) of FOXP3 mRNA. Using lentiviral transduction of fresh cord blood T cells, we demonstrated that miR-31 and miR-21 had an effect on FOXP3 expression levels. We showed that miR-31 negatively regulates FOXP3 expression by binding directly to its potential target site in the 3, UTR of FOXP3 mRNA. We next demonstrated that miR-21 acted as a positive, though indirect, regulator of FOXP3 expression. Transduction of the remaining three miR had no direct effect on FOXP3 expression or on the phenotype and will remain the subject of future investigations. In conclusion, not only have we identified and validated a miR signature for human natural Treg, but also unveiled some of the mechanisms by which this signature was related to the control of FOXP3 expression in these cells. [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] Dysfunction of CD4+CD25high T regulatory cells in patients with recurrent aphthous stomatitisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2008Natalia Lewkowicz Background:, Recurrent aphthous stomatitis (RAS) is a chronic inflammatory disease of unknown etiology characterized by recurring formation of painful oral ulcers. RAS may result from oral epithelium damage caused by T-cell-mediated immune response. CD4+CD25+ T regulatory (Treg) cells suppress proliferation and effector functions of other immune cells, and therefore are crucial in regulating the immune response. Methods:, We tested the function of peripheral CD4+CD25high Treg cells in active RAS through their ability to inhibit proliferation and cytokine production of conventional CD4+ T cells. We also attempted to detect the presence of FOXP3 and indoleamine 2,3-dioxygenase (IDO) mRNA in the lesional and non-lesional oral mucosa of RAS patients and healthy individuals using real-time PCR assay. Results:, Treg cells derived from RAS patients were less efficient in the suppression of cytokine production of CD4+ T effector cells than Treg cells from healthy individuals. Moreover, in RAS, Treg cells were nearly twice less potent in the inhibition of CD4+CD25, T cell proliferation than in healthy donors. Furthermore, we have demonstrated the decreased proportion of CD4+CD25+FOXP3+ Treg cells in peripheral blood of RAS patients compared with controls. We failed to detect FOXP3 mRNA, while IDO mRNA expression was decreased in non-lesional mucosa biopsies from RAS patients compared with ulcer biopsies or normal mucosa from healthy donors. Conclusions:, These findings suggest that CD4+CD25high Treg cells are both functionally and quantitatively compromised in RAS and that decreased constitutive expression of IDO in oral mucosa in RAS may lead to the loss of local immune tolerance. [source] ORIGINAL ARTICLE: Imbalance of T-cell Transcription Factors Contributes to the Th1 Type Immunity Predominant in Pre-eclampsiaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Zhou Jianjun Problem, Extensive studies have demonstrated that Th1 type immunity is predominant in pre-eclampsia, but there is little concern with regard to the intracellular mechanisms behind this initial T-cell polarization. In this study, we investigated whether the imbalance of the T-cell transcription factors contributes to it. Method of study, A total of 15 pre-eclamptic patients and 15 healthy pregnant women were enrolled in this study. The expression levels of transcription factors for Th1 (T-bet), Th2 (GATA3), Th17 (RORc) and Treg (FOXP3) cells, together with the Th1/Th2 status, were simultaneously investigated in both peripheral blood mononuclear cells (PBMCs) and decidua. Results, The expression levels of FOXP3 mRNA were decreased in both PBMCs and decidua from pre-eclamptic patients compared with healthy pregnant women (P < 0.05), and T-bet mRNA and RORc mRNA were significantly increased (P < 0.05), while Th1/Th2 balance shifted toward the Th1 immunity. Furthermore, there was a negative correlation between FOXP3 mRNA and Th1 cells (P < 0.05), and the expression level of T-bet mRNA correlated strongly with Th1 cells (P < 0.05). Conclusion, Decreased expression of FOXP3 mRNA and increased expression of T-bet mRNA may contribute to Th1 type immunity predominant in pre-eclampsia. [source] FOXP3 Expression in Human Kidney Transplant Biopsies Is Associated with Rejection and Time Post Transplant but Not with Favorable OutcomesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2008S. Bunnag Expression of the transcription factor forkhead box P3 (FOXP3) in transplant biopsies is of interest due to its role in a population of regulatory T cells. We analyzed FOXP3 mRNA expression using RT-PCR in 83 renal transplant biopsies for cause in relationship to histopathology, clinical findings and expression of pathogenesis-based transcript sets assessed by microarrays. FOXP3 mRNA was higher in rejection (T-cell and antibody-mediated) than nonrejection. Surprisingly, some native kidney controls also expressed FOXP3 mRNA. Immunostaining for FOXP3 was consistent with RT-PCR, showing interstitial FOXP3+ lymphocytes, even in some native kidney controls. FOXP3 expression correlated with interstitial inflammation, tubulitis, interstitial fibrosis, tubular atrophy, C4d positivity, longer time posttransplant, younger donors, class II panel reactive antibody >20% and transcript sets reflecting inflammation and injury, but unlike these features was time dependent. In multivariate analysis, higher FOXP3 mRNA was independently associated with rejection, T-cell-associated transcripts, younger donor age and longer time posttransplant. FOXP3 expression did not correlate with favorable graft outcomes, even when the analysis was restricted to biopsies with rejection. Thus FOXP3 mRNA expression is a time-dependent feature of inflammatory infiltrates in renal tissue. We hypothesize that time-dependent entry of FOXP3-positive cells represents a mechanism for stabilizing inflammatory sites. [source] Distinct regulatory roles of transforming growth factor-, and interleukin-4 in the development and maintenance of natural and induced CD4+ CD25+ Foxp3+ regulatory T cellsIMMUNOLOGY, Issue 1pt2 2009Jana Prochazkova Summary The development and function of CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) are strictly regulated by cytokines. Here we show that transforming growth factor-, (TGF-,) and interleukin-4 (IL-4) play a crucial and antagonistic role in the development of Tregs. Additionally, these cytokines also have distinct effects on the maintenance of natural (nTregs) and antigen-induced (iTregs) Tregs. Using double-staining and tracking of proliferation of purified and carboxyflourescein succinimidyl ester (CFSE)-labelled mouse T-cell subpopulations we demonstrated that CD4+ CD25+ Foxp3+ iTregs develop upon alloantigenic stimulation in the presence of TGF-, exclusively from CD4+ CD25, Foxp3, precursors. Both the induction of Foxp3 expression and Treg proliferation were prevented when the cells were stimulated in the presence of IL-4. By contrast, nTregs did not proliferate in the presence of the antigen and TGF-,, and partially lost their Foxp3 expression. IL-4 not only prevented the development of iTregs, but also down-regulated the level of Foxp3 mRNA and decreased the number of Foxp3+ cells in a population of iTregs. Further analyses proved that IL-4 decreased the expression of Foxp3 only in a population of iTregs, whereas it substantially supported the survival of nTregs. Functional experiments showed that Tregs induced in the presence of alloantigen and TGF-, inhibited, on a per-cell basis, cell proliferation comparably to nTregs, and their suppressive capacity was not modulated by IL-4. These data suggest that TGF-, and IL-4 differentially regulate the development of Tregs and distinctly sustain Foxp3 expression and the number of nTregs and iTregs, but have no influence on the suppressive activity of Tregs on a per-cell basis. [source] A Possible Role of CD4+CD25+ T Cells as Well as Transcription Factor Foxp3 in the Dysregulation of Allergic RhinitisTHE LARYNGOSCOPE, Issue 5 2007Geng Xu MD Abstract Background: Allergic rhinitis (AR) is a Th2 predominant disease, and its pathogenic mechanism is still poorly understood. CD4+CD25+ T cells account for approximately 5% to 10% peripheral CD4+ T cells and has been shown to regulate the activation of effector T cells in the periphery. The activity of CD4+CD25+ T cells is associated with the transcription factor Foxp3. The present study aimed to evaluate the possible role of CD4+CD25+ T cells as well as Foxp3 in the pathogenesis of AR. Methods: Nasal tissues and peripheral blood mononuclear cells (PBMCs) were obtained from 17 patients with AR and 11 control subjects. Foxp3 was detected in nasal tissues by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR). CD4+CD25+ T cells and Foxp3 were evaluated in PBMCs by using flow cytometry. Concentrations of interleukin-2 (IL-2) and interferon-, (IFN-,) were measured by enzyme-linked immunosorbent assay (ELISA) in cultured PBMCs in the presence or absence of stimulation with phorbol ester (PMA) and Ionomycin. Results: The numbers of Foxp3+ cells was 129.5 ± 35.6 and 44.2 ± 20.5 cells/mm2 in nasal mucosa of two groups (P < .05). There were less Foxp3+ lymphocytes and decreased Foxp3 mRNA in AR compared with the control (P < .05). The frequencies of the CD4+CD25+ population in PBMCs of two groups were 1.99 ± 0.95% and 3.55 ± 1.27% (P < .05). There was significant difference in the frequencies of the Foxp3+CD4+ CD25+ population (1.81 ± 0.77 vs 3.37 ± 1.04, P < .05) and mean fluorescence intensity (MFI) of Foxp3 (5.93 ± 2.64 vs 11.72 ± 4.29, P < .05) in PBMCs of two groups. After stimulation, the concentrations of IL-2 and IFN-, were 182.72 ± 85.11 pg/mL and 348.94 ± 151.88 pg/mL in PBMCs with AR, while those were 90.6 ± 61.5 pg/mL and 155.64 ± 68.33 pg/mL in controls (P < .05). Conclusion: Our results indicate that CD4+ CD25+ regulatory T cells as well as Foxp3 may play a crucial role in immunological imbalance of AR. These findings suggest that increasing Foxp3 and CD4+CD25+ T cells have the potential to be new therapeutic targets for the treatment of AR. [source] | ||||||||||