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Langerhans Cells (Langerhan + cell)
Kinds of Langerhans Cells Terms modified by Langerhans Cells Selected AbstractsChronic Ethanol Consumption Decreases Murine Langerhans Cell Numbers and Delays Migration of Langerhans Cells as Well as Dermal Dendritic CellsALCOHOLISM, Issue 4 2008Kristin J. Ness Background:, Chronic alcoholics experience increased incidence and severity of infections, the mechanism of which is incompletely understood. Dendritic cells (DC) migrate from peripheral locations to lymph nodes (LN) to initiate adaptive immunity against infection. Little is known about how chronic alcohol exposure affects skin DC numbers or migration. Methods:, Mice received 20% EtOH in the drinking water for up to 35 weeks. Baseline Langerhans cell (LC) and dermal DC (dDC) numbers were enumerated by immunofluorescence (IF). LC repopulation after inflammation was determined following congenic bone marrow (BM) transplant and ultraviolet (UV) irradiation. Net LC loss from epidermis was determined by IF following TNF-, or CpG stimulation. LC and dDC migration into LN was assessed by flow cytometry following epicutaneous FITC administration. Results:, Chronic EtOH consumption caused a baseline reduction in LC but not dDC numbers. The deficit was not corrected following transplantation with non-EtOH-exposed BM and UV irradiation, supporting the hypothesis that the defect is intrinsic to the skin environment rather than LC precursors. Net loss of LC from epidermis following inflammation was greatly reduced in EtOH-fed mice versus controls. Ethanol consumption for at least 4 weeks led to delayed LC migration into LN, and consumption for at least 8 weeks led to delayed dDC migration into LN following epicutaneous FITC application. Conclusions:, Chronic EtOH consumption causes decreased density of epidermal LC, which likely results in decreased epidermal immunosurveillance. It also results in altered migratory responsiveness and delayed LC and dDC migration into LN, which likely delays activation of adaptive immunity. Decreased LC density at baseline appears to be the result of an alteration in the skin environment rather than an intrinsic LC defect. These findings provide novel mechanisms to at least partially explain why chronic alcoholics are more susceptible to infections, especially those following skin penetration. [source] DNA Damage, Apoptosis and Langerhans Cells,Activators of UV-induced Immune Tolerance,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2008Laura Timares Solar UVR is highly mutagenic but is only partially absorbed by the outer stratum corneum of the epidermis. UVR can penetrate into the deeper layers of the epidermis, depending on melanin content, where it induces DNA damage and apoptosis in epidermal cells, including those in the germinative basal layer. The cellular decision to initiate either cellular repair or undergo apoptosis has evolved to balance the acute need to maintain skin barrier function with the long-term risk of retaining precancerous cells. Langerhans cells (LCs) are positioned suprabasally, where they may sense UV damage directly, or indirectly through recognition of apoptotic vesicles and soluble mediators derived from surrounding keratinocytes. Apoptotic vesicles will contain UV-induced altered proteins that may be presented to the immune system as foreign. The observation that UVR induces immune tolerance to skin-associated antigens suggests that this photodamage response has evolved to preserve the skin barrier by protecting it from autoimmune attack. LC involvement in this process is not clear and controversial. We will highlight some basic concepts of photobiology and review recent advances pertaining to UV-induced DNA damage, apoptosis regulation, novel immunomodulatory mechanisms and the role of LCs in generating antigen-specific regulatory T cells. [source] Decrease in Langerhans Cells and Increase in Lymph Node Dendritic Cells Following Chronic Exposure of Mice to Suberythemal Doses of Solar Simulated RadiationPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2005Pauline McLoone ABSTRACT Exposure of certain strains of mice to ultraviolet radiation (UVR) causes suppression of some innate and adaptive immune responses. One such consequence of acute UVB exposure is a reduction in the number of Langerhans cells (LC) in the epidermis and an increase in dendritic cells (DC) in lymph nodes draining the irradiated skin sites. Exposure to chronic UVB irradiation also has effects on the immune system, but it is unknown what effects are caused by repeated doses of solar simulated radiation (SSR). Consequently, the main aims of the present study were to determine whether repeated exposure to low doses of SSR would lead to similar changes in these cell populations and whether chronic doses of SSR activate a protective photoadaptation mechanism. Groups of C3H/HeN mice were irradiated daily with 3.7 J/cm2 SSR from Cleo Natural lamps for 2, 10, 20, 30 or 60 days. Further groups of mice received an additional dose of 7.4 J/cm2 SSR on days 2, 10, 30 or 60 to test for photoadaptation. The numbers of LC in the epidermis and DC in the lymph nodes draining irradiated skin sites were counted 24 h after the final irradiation. With the exception of mice irradiated for only 2 days, LC were significantly reduced throughout the chronic irradiation protocol, and no recovery occurred. DC numbers were significantly increased in the draining lymph nodes of mice irradiated for 20 days and 60 days. [source] Epidermal Langerhans Cells Promote Skin Allograft Rejection in Mice With NF-,B-impaired T CellsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2008L. L. Molinero T cells play a major role in the acute rejection of transplanted organs. Using mice transgenic for a T-cell-restricted NF-,B super-repressor (I,B,,N-Tg mice), we have previously shown that T-cell-NF-,B is essential for the acute rejection of cardiac but not skin allografts. In this study, we investigated the mechanism by which skin grafts activate I,B,,N-Tg T cells. Rejection was not due to residual T-cell-NF-,B activity as mice with p50/p52,/, T cells successfully rejected skin grafts. Rather, skin but not cardiac allografts effectively induced proliferation of graft-specific I,B,,N-Tg T cells. Rejection of skin grafts by I,B,,N-Tg mice was in part dependent on the presence of donor Langerhans cells (LC), a type of epidermal dendritic cells (DC), as lack of LC in donor skin grafts resulted in prolongation of skin allograft survival and injection of LC at the time of cardiac transplantation was sufficient to promote cardiac allograft rejection by I,B,,N-Tg mice. Our results suggest that LC allow NF-,B-impaired T cells to reach an activation threshold sufficient for transplant rejection. The combined blockade of T-cell-NF-,B with that of alternative pathways allowing activation of NF-,B-impaired T cells may be an effective strategy for tolerance induction to highly immunogenic organs. [source] A Note on Langerhans Cells in the Oesophagus Epithelium of Domesticated MammalsANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2 2010W. Meyer With 3 figures Summary Using the zinc-iodide osmium tetroxide (ZIO) method, TEM and immunohistochemistry (for CD1a and langerin), the study demonstrates Langerhans cells in the oesophageal epithelium of domesticated mammals (herbivores: horse, cattle, goat; omnivores: pig, dog, laboratory rat; carnivores: cat), although with variations between the species. The ZIO method and TEM showed this cell type in the cat and, sporadically, in the horse; CD1a (+) Langerhans cells were demonstrated in the ovine, porcine and murine oesophagus. Positive staining for langerin was detected in single cells of the caprine, canine, murine and feline oesophagus and more distinct in almost all the cell layers of the equine and porcine oesophagus epithelium. The findings are discussed comparing specifically the results for CD1a and langerin, whereby the latter C-type lectin may be of importance in species with a rather thick oesophagus epithelium, such as that present in the plantivorous and most of the omnivorous animals, where antigenic pressure is reduced. [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] Chronic Ethanol Consumption Decreases Murine Langerhans Cell Numbers and Delays Migration of Langerhans Cells as Well as Dermal Dendritic CellsALCOHOLISM, Issue 4 2008Kristin J. Ness Background:, Chronic alcoholics experience increased incidence and severity of infections, the mechanism of which is incompletely understood. Dendritic cells (DC) migrate from peripheral locations to lymph nodes (LN) to initiate adaptive immunity against infection. Little is known about how chronic alcohol exposure affects skin DC numbers or migration. Methods:, Mice received 20% EtOH in the drinking water for up to 35 weeks. Baseline Langerhans cell (LC) and dermal DC (dDC) numbers were enumerated by immunofluorescence (IF). LC repopulation after inflammation was determined following congenic bone marrow (BM) transplant and ultraviolet (UV) irradiation. Net LC loss from epidermis was determined by IF following TNF-, or CpG stimulation. LC and dDC migration into LN was assessed by flow cytometry following epicutaneous FITC administration. Results:, Chronic EtOH consumption caused a baseline reduction in LC but not dDC numbers. The deficit was not corrected following transplantation with non-EtOH-exposed BM and UV irradiation, supporting the hypothesis that the defect is intrinsic to the skin environment rather than LC precursors. Net loss of LC from epidermis following inflammation was greatly reduced in EtOH-fed mice versus controls. Ethanol consumption for at least 4 weeks led to delayed LC migration into LN, and consumption for at least 8 weeks led to delayed dDC migration into LN following epicutaneous FITC application. Conclusions:, Chronic EtOH consumption causes decreased density of epidermal LC, which likely results in decreased epidermal immunosurveillance. It also results in altered migratory responsiveness and delayed LC and dDC migration into LN, which likely delays activation of adaptive immunity. Decreased LC density at baseline appears to be the result of an alteration in the skin environment rather than an intrinsic LC defect. These findings provide novel mechanisms to at least partially explain why chronic alcoholics are more susceptible to infections, especially those following skin penetration. [source] Irritant threshold and histological response of epidermis to irritant applicationCONTACT DERMATITIS, Issue 5-6 2004H. R. Smith Individuals vary in their ability to react to irritants, which can be demonstrated for sodium lauryl sulfate (SLS) using the irritant threshold (IT) test. We aimed to study whether the histological and immunohistochemical features of the skin following SLS exposure varied with subject's IT. 8 subjects were recruited. Their IT was measured. Biopsies were taken after 2 hr and 4 hr of occlusion with 20% SLS and control. The specimens were stained with haematoxylin and eosin and for Langerhans cells. At 4-hr, low-threshold subjects developed changes to a greater extent than high-threshold subjects. The relationship of histological reaction to IT could be related to a differential pro-inflammatory cytokine response in subjects. Low IT has been previously associated with a tumour necrosis factor alpha promoter region polymorphism. [source] A two-step model for Langerhans cell migration to skin-draining LNEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008Eduardo J. Villablanca Abstract Although the role of Langerhans cells (LC) in skin immune responses is still a matter of debate, it is known that LC require the chemokine receptor CCR7 for migrating to skin-draining LN. A report in the current issue of the European Journal of Immunology unfolds some of the intricacies of LC migration, showing that LC need CXCR4, but not CCR7, for their migration from the epidermis to the dermis. Thus, LC migration to skin-draining LN occurs in two distinct phases: a first step from the epidermis to the dermis regulated by CXCR4 and a second CCR7-dependent step from the dermis to LN. Here we discuss the potential implications of this new two-step LC migration paradigm. [source] Dendritic cells: Understanding immunogenicityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue S1 2007Ralph Abstract The impetus for the discovery of dendritic cells in 1972 was to understand immunogenicity, the capacity of an antigenic substance to provoke immunity. During experiments to characterize "accessory" cells that enhanced immunity, we spotted unusual stellate cells in mouse spleen. They had a distinct capacity to form and retract processes or dendrites and were named dendritic cells (DC). DC proved to be different from other cell types and to be peculiarly immunogenic when loaded with antigens. When Langerhans cells were studied, immunogenicity was found to involve two steps: antigen presentation by immature DC and maturation to elicit immunity. Antigen-bearing DC were also immunogenic in vivo and were therefore termed "nature's adjuvants". Several labs then learned to generate large numbers of DC from progenitors, which accelerated DC research. Tolerogenicity via DC, including the control of foxp3+ suppressor T cells, was recently discovered. Two areas of current research that I find intriguing are to identify mechanisms for antigen uptake and processing, and for the control of different types of immunity and tolerance. These subjects should be studied in vivo with clinically relevant antigens, so that the activities of DC can be better integrated into the prevention and treatment of disease in patients. [source] Bone marrow-derived cells expand memory CD8+ T,cells in response to viral infections of the lung and skinEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2006Gabrielle Abstract While naive CD8+ T,cells have been shown to require bone marrow-derived dendritic cells (DC) to initiate immunity, such a requirement for memory CD8+ T,cells has had limited assessment. By generating bone marrow chimeras that express the appropriate antigen-presenting molecules on either radiation-sensitive bone marrow-derived or radiation-resistant non-bone marrow-derived compartments, we showed that both primary and secondary immune responses to influenza virus infection of the lung were initiated in the draining LN. This required cells of bone marrow origin, most likely DC, for optimal expansion within the secondary lymphoid compartment. This was similarly the case with HSV-1 infection of the skin. As Langerhans cells are radioresistant, unlike other DC populations, these studies also demonstrate that the radiosensitive DC responsible for secondary expansion of HSV-specific memory are not Langerhans cells. [source] Expression of milk fat globule epidermal growth factor,8 in immature dendritic cells for engulfment of apoptotic cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2004Kay Miyasaka Abstract Milk fat globule epidermal growth factor,8 (MFG-E8) is a protein that stimulates the engulfment of apoptotic cells by phagocytes. Here, we show that mouse immature dendritic cells (DC) generated in vitro by culturing bone marrow progenitors in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), and Langerhans cells present in the skins, expressed MFG-E8. Bone marrow-derived macrophages generated by M-CSF did not express MFG-E8. MFG-E8 expressed in immature DC was found to be secreted as exosomes. The expression of MFG-E8 was significantly suppressed when the immature DC were induced to mature by treating them with lipopolysaccharides. This expression of MFG-E8 was well correlated with the ability of the cells to engulf apoptotic cells. That is,immature DC phagocytosed apoptotic cells more efficiently than did mature DC or bone marrow-derived macrophages. The ability of immature DC to engulf apoptotic cells was severely reduced when the immature DC were prepared from MFG-E8-deficient mice. These results indicated that MFG-E8 plays an essential role in the engulfment of apoptotic cells by bone marrow-derived immature DC. [source] TNF-, induces the generation of Langerin/(CD207)+ immature Langerhans-type dendritic cells from both CD14,CD1a, and CD14+CD1a, precursors derived from CD34+ cord blood cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2003Jean-François Arrighi Abstract CD34+ cell-derived hematopoietic precursors amplified with FLT3-ligand, thrombopoietin and stem cell factor became, after a 6-day induction with GM-CSF, IL-4 and TGF-,1, HLA-DR+, CD1a+, CD83,, CD86,, CD80, cells. A fraction of them expressed Langerin, Lag, and E-cadherin, resembling epidermal Langerhans cells (LC). TNF-, addedfor the last 3,days only marginally induced CD83 expression, but strikingly increased the proportion of immature Langerin+CD83, LC. Langerin+CD83+ and Langerin+CD83, cells were functionally distinct, the former internalizing less efficiently Langerin than the latter. Both CD1a,CD14, and CD1a,CD14+ cells sorted from FLT3-ligand, thrombopoietin and stem cell factor cultures responded to TNF-, by an increase of Langerin+ cells. Thus, TNF-, rescued LC precursors irrespective of their commitment to the monocytic lineage. When added to GM-CSF, IL-4 and TGF,,1 containing-cultures, LPS or IL-1, also induced significant numbers of Langerin+CD83, immature cells displaying a low allostimulatory activity, while CD40-ligand largely promoted highly allostimulatory Langerin,CD83+ cells. Altogether, these data show that in contrast to CD40-ligand, which induced LC maturation even in presence of TGF-,1, nonspecific proinflammatory factors such as TNF-,, IL-1, or LPS, essentially induced immature LC generation, and little cell activation in the presence of TGF-,1. [source] About the cutaneous targets of bexarotene in CTCL patientsEXPERIMENTAL DERMATOLOGY, Issue 8 2010Anne Chantal Knol Please cite this paper as: About the cutaneous targets of bexarotene in CTCL patients. Experimental Dermatology 2010; 19: e299,e301. Abstract:, There are several approved therapies for cutaneous T-cell lymphoma (CTCL). The retinoids are one of the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. Bexarotene has been demonstrated to act on malignant T-cells by inducing their apoptosis, but nothing is known about its role on keratinocytes and Langerhans cells. Immunohistochemical analysis using CD1a, HLA-DR, ICAM-1 (activation markers), CD95 and CD40 (apoptosis markers) was conducted on frozen sections of bexarotene-exposed cutaneous explants and skin biopsy specimens from patients treated with bexarotene. None of the studied markers was significantly modulated both on cutaneous explants and on skin biopsy specimens after treatment with bexarotene, compared to controls. Langerhans cells and keratinocytes do not appear to play a central role in the therapeutic control of CTCL by bexarotene therapy. The main bexarotene's target thus remains T-cells by inducing their apoptosis, a mechanism that is different from the other retinoids used in CTCL. [source] The human skin/chick chorioallantoic membrane model accurately predicts the potency of cosmetic allergensEXPERIMENTAL DERMATOLOGY, Issue 4 2009Dan Slodownik Abstract:, The current standard method for predicting contact allergenicity is the murine local lymph node assay (LLNA). Public objection to the use of animals in testing of cosmetics makes the development of a system that does not use sentient animals highly desirable. The chorioallantoic membrane (CAM) of the chick egg has been extensively used for the growth of normal and transformed mammalian tissues. The CAM is not innervated, and embryos are sacrificed before the development of pain perception. The aim of this study was to determine whether the sensitization phase of contact dermatitis to known cosmetic allergens can be quantified using CAM-engrafted human skin and how these results compare with published EC3 data obtained with the LLNA. We studied six common molecules used in allergen testing and quantified migration of epidermal Langerhans cells (LC) as a measure of their allergic potency. All agents with known allergic potential induced statistically significant migration of LC. The data obtained correlated well with published data for these allergens generated using the LLNA test. The human-skin CAM model therefore has great potential as an inexpensive, non-radioactive, in vivo alternative to the LLNA, which does not require the use of sentient animals. In addition, this system has the advantage of testing the allergic response of human, rather than animal skin. [source] Immunohistochemistry and in situ hybridization in the study of human skin melanocytesEXPERIMENTAL DERMATOLOGY, Issue 3 2007Thierry Passeron Abstract: Although keratinocytes are the most numerous type of cell in the skin, melanocytes are also key players as they produce and distribute melanin that protects the skin from ultraviolet (UV) radiation. In vitro experiments on melanocytic cell lines are useful to study melanogenesis and their progression towards melanoma. However, interactions of melanocytes with keratinocytes and with other types of cells in the skin, such as fibroblasts and Langerhans cells, are also crucial. We describe two techniques, immunohistochemistry (IHC) and tissue in situ hybridization (TISH), that can be used to identify and study melanocytes in the skin and their responses to UV or other stimuli in situ. We describe a practical method to localize melanocytic antigens on formalin-fixed, paraffin-embedded tissue sections and in frozen sections using indirect immunofluorescence with conjugated secondary antibodies. In addition, we detail the use of TISH and its combination with IHC to study mRNA levels of genes expressed in the skin at cellular resolution. This methodology, along with relevant tips and troubleshooting items, are important tools to identify and study melanocytes in the skin. [source] Immune response modifiers , mode of actionEXPERIMENTAL DERMATOLOGY, Issue 5 2006Meinhard Schiller Abstract:, The innate immune system governs the interconnecting pathways of microbial recognition, inflammation, microbial clearance, and cell death. A family of evolutionarily conserved receptors, known as the Toll-like receptors (TLRs), is crucial in early host defense against invading pathogens. Upon TLR stimulation, nuclear factor-,B activation and the interferon (IFN)-regulatory factor 3 pathway initiate production of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-,, and production of type I IFNs (IFN-, and IFN-,), respectively. The innate immunity thereby offers diverse targets for highly selective therapeutics, such as small molecular synthetic compounds that modify innate immune responses. The notion that activation of the innate immune system is a prerequisite for the induction of acquired immunity raised interest in these immune response modifiers as potential therapeutics for viral infections and various tumors. A scenario of dermal events following skin cancer treatment with imiquimod presumably comprises (i) an initial low amount of pro-inflammatory cytokine secretion by macrophages and dermal dendritic cells (DCs), thereby (ii) attracting an increasing number type I IFN-producing plasmacytoid DCs (pDCs) from the blood; (iii) Langerhans cells migrate into draining lymph nodes, leading to an increased presentation of tumor antigen in the draining lymph node, and (iv) consequently an increased generation of tumor-specific T cells and finally (v) an accumulation of tumoricidal effector cells in the treated skin area. The induction of predominately T helper (Th)1-type cytokine profiles by TLR agonists such as imiquimod might have further benefits by shifting the dominant Th2-type response in atopic diseases such as asthma and atopic dermatitis to a more potent Th1 response. [source] Connections between nerve endings and epidermal cells: are they synapses?EXPERIMENTAL DERMATOLOGY, Issue 1 2004Yannick Chateau Abstract: Based on electron microscopy and confocal scanning microscopy, contacts between sensory axons and the cells of the epidermis have been described: with keratinocytes, Langerhans cells, melanocytes and Merkel cells. We would like to initiate a debate on this question: "Are neuro-epidermal connections synapses?". Anatomically, neuro-epidermal junctions can be considered as synapses in our opinion. If neuro-epidermal junctions are synapses, they probably belong to the family of en passant synapses, with nerve endings passing along epidermal cells and occasionally connecting to them. In conclusion, we suggest that neuro-epidermal junctions could be considered as true synapses, but this does not exclude non synaptic interactions. [source] Solar-simulating irradiation of the skin of human subjects in vivo produces Langerhans cell responses distinct from irradiation ex vivo and in vitroEXPERIMENTAL DERMATOLOGY, Issue 4 2000J. K. Laihia Abstract: It has been postulated that Langerhans cells (LC) provide tolerogenic signals in the local impairment of cutaneous immune functions and antigen-specific tolerance induced by UV radiation. Studies in vitro and ex vivo have indicated that UV radiation may down-regulate the expression of costimulatory molecules on LC, leading to reduced antigen-presenting function. In contrast, we recently observed an up-regulatory stage in the number of human epidermal LC with induced expression of B7 costimulatory molecules 12,24 h after solar-simulating UV radiation (SSR) in vivo. To examine the apparent discrepancy between the observed human LC responses in vitro, ex vivo and in vivo, we compared the three protocols in a parallel fashion. The intact skin as well as skin explants and epidermal cell suspensions from the same individuals were irradiated with a single erythematogenic dose of SSR. The expression of cell surface markers in the epidermal cells was analysed with flow cytometry 24 h later. The number of CD1a+/HLA-DR+ LC increased post-SSR in vivo by a factor of 2.8±0.4, whereas in irradiated skin explants ex vivo or in cell suspensions in vitro, reduced numbers were seen. HLA-DR expression intensities were found to have increased on DR+ and CD1a+/DR+ cells in vivo. Similarly, SSR induced B7-2 (CD86) expression in CD1a+ cells significantly in vivo (P=0.031) but reduced the expression ex vivo or in vitro. We conclude that the early up-regulatory stage of human LC number and membrane markers, recorded at 24 h after a single exposure to SSR, is exclusively an in vivo phenomenon. [source] Epicutaneous immunization converts subsequent and established antigen-specific T helper type 1 (Th1) to Th2-type responsesIMMUNOLOGY, Issue 1 2006Jessica Strid Summary Epicutaneous immunization is a potential novel technique for topical vaccine delivery. It targets the immunologically rich milieu of the skin while having the advantage of being a non-invasive immunization procedure. By disrupting the stratum corneum of the epidermis a natural adjuvant effect can be achieved through activation of resident Langerhans cells. This negates the normal need for co-application of noxious adjuvants. Epicutaneous immunization on barrier-disrupted skin induces potent antigen-specific systemic immunity with a strong T helper type 2 (Th2) bias. We show here that epicutaneous immunization enhances the vigour of a subsequent T-cell response to the same antigen. The induced systemic Th2 response prevents the development of Th1 responses induced through injection of antigen in complete Freund's adjuvant (CFA). Prior epicutaneous immunization results in reduced production of antigen-specific interferon-, and immunoglobulin G2a (IgG2a) and enhanced interleukin-4, IgG1 and IgE responses to immunization with CFA. Moreover, epicutaneous immunization converts an established Th1 response to a Th2 response, as demonstrated by the specific reduction of interferon-, and IgG2a and the enhancement of interleukin-4 and IgE. This Th2 dominance of epicutaneous immunization may have direct therapeutic application as an immune-modulating procedure in Th1-dominant diseases such as autoimmune rheumatoid arthritis, type 1 diabetes, Hashimoto's thyroiditis and multiple sclerosis. [source] Major histocompatibility complex class II, fetal skin dendritic cells are potent accessory cells of polyclonal T-cell responsesIMMUNOLOGY, Issue 2 2000A. Elbe-Bürger Summary Whereas dendritic cells (DC) and Langerhans cells (LC) isolated from organs of adult individuals express surface major histocompatibility complex (MHC) class II antigens, DC lines generated from fetal murine skin, while capable of activating naive, allogeneic CD8+ T cells in a MHC class I-restricted fashion, do not exhibit anti-MHC class II surface reactivity and fail to stimulate the proliferation of naive, allogeneic CD4+ T cells. To test whether the CD45+ MHC class I+ CD80+ DC line 80/1 expresses incompetent, or fails to transcribe, MHC class II molecules, we performed biochemical and molecular studies using Western blot and polymerase chain reaction analysis. We found that 80/1 DC express MHC class II molecules neither at the protein nor at the transcriptional level. Ultrastructural examination of these cells revealed the presence of a LC-like morphology with indented nuclei, active cytoplasm, intermediate filaments and dendritic processes. In contrast to adult LC, no LC-specific cytoplasmic organelles (Birbeck granules) were present. Functionally, 80/1 DC in the presence, but not in the absence, of concanavalin A and anti-T-cell receptor monoclonal antibodies stimulated a vigorous proliferative response of naive CD4+ and CD8+ T cells. Furthermore, we found that the anti-CD3-induced stimulation of naive CD4+ and CD8+ T cells was critically dependent on the expression of Fc,R on 80/1 DC and that the requirement for co-stimulation depends on the intensity of T-cell receptor signalling. [source] A quantitative study of epidermal Langerhans cells in cutaneous leishmaniasis caused by Leishmania tropicaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2004Simin Meymandi MD Objective, The purpose of this study was to characterize the number and distribution of epidermal Langerhans cells in different clinical forms of dry-type cutaneous leishmaniasis (CL). Methods, Sixteen cases of dry-type cutaneous leishmaniasis caused by Leishmania tropica were studied. These cases were classified clinically as five cases of acute leishmaniasis with indurated papules, nodules and plaques with central crust formation and duration < 2 years, six cases of lupoid leishmaniasis with characteristic papules around previous scars of cutaneous leishmaniasis with duration > 2 years, and five cases of chronic nonlupoid type with nonhealing lesions of duration > 2 years. Paraffin-embedded blocks were stained with hematoxylin and eosin (H&E) and stained immunohistochemically for CD1a. Results, The number of Langerhans cells per millimeter length of epidermis was increased in acute cases compared to chronic and lupoid cases. Conclusions, Lesions of acute leishmaniasis contain the greatest amounts of antigen for presentation, so Langerhans cells increase in number and in trafficking to present antigens derived from Leishman bodies to the cellular immune system. In chronic leishmaniasis, the Langerhans cell population is reduced, perhaps because of exhaustion of the source of Langerhans cells, or because of reduced response to modified antigen. [source] Demonstration of Birbeck (Langerhans cells) granules in the normal chicken epidermisJOURNAL OF ANATOMY, Issue 4 2001ARMANDO PÉREZ-TORRES Mammalian Langerhans cells (LC) are epidermal dendritic cells which originate in bone marrow and migrate toward the T cell area of lymph nodes, where they act as professional antigen-presenting cells. A variety of cell surface markers, such as the ectoenzyme adenosine triphosphatase (ATPase), Ia and CD1a antigens, have been used extensively to identify LC. Ultrastructural identification of this cell type in the mammalian epidermis is made by the demonstration of a typical and unique cytoplasmic organelle, the Birbeck granule (BG). Although we had earlier demonstrated the coexpression of ATPase and Ia antigens on epidermal dendritic cells of the chicken epidermis, the presence of the BG has not previously been documented. The aim of the present study was to investigate whether chicken epidermal LC-like cells possess an organelle similar to the BG, and thus to complete their identification. Our findings are the first demonstration of characteristic rod-shaped, racket-shaped and disc-shaped intracytoplasmic organelles, morphologically similar to the mammalian BG, in avian LC. [source] Determinants of skin sensitisation potentialJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2008David W. Roberts Abstract Skin sensitisation is an important toxicological endpoint. The possibility that chemicals used in the workplace and in consumer products might cause skin sensitisation is a major concern for individuals, for employers and for marketing. In European REACH (Registration, Evaluation, and Authorisation of Chemicals) legislation, the sensitising potential should therefore be assessed for chemicals below the 10 ton threshold. Development of methods for prediction of skin sensitisation potential without animal testing has been an active research area for some time, but has received further impetus with the advent of REACH and the EU Cosmetics Directive (EU 2003). This paper addresses the issue of non-animal based prediction of sensitisation by a mechanistic approach. It is known that the sequence of molecular, biomolecular and cellular events between exposure to a skin sensitiser and development of the sensitised state involves several stages, in particular penetration through the stratum corneum, covalent binding to carrier protein, migration of Langerhans cells, presentation of the antigen to naïve T-cells. In this paper each of these stages is considered with respect to the extent to which it is dependent on the chemical properties of the sensitiser. The evidence suggests that, although penetration of the stratum corneum, stimulation of migration and maturation of Langerhans cells, and antigen recognition are important events in the induction of sensitisation, except in certain specific circumstances they can be taken for granted. They are not important factors in determining whether a compound will be a sensitiser or not, nor are they important factors in determining how potent one sensitiser will be relative to another. The ability to bind covalently to carrier protein is the major structure-dependent determinant of skin sensitisation potential. A chemistry-based prediction strategy is proposed involving reaction mechanistic domain assignment, reactivity and hydrophobicity determination, and application of quantitative mechanistic modelling (QMM) or read-across. Copyright © 2007 John Wiley & Sons, Ltd. [source] Protective effects of a topical antioxidant mixture containing vitamin C, ferulic acid, and phloretin against ultraviolet-induced photodamage in human skinJOURNAL OF COSMETIC DERMATOLOGY, Issue 4 2008Christian Oresajo PhD Summary Background, Ultraviolet (UV) irradiation of the skin leads to acute inflammatory reactions, such as erythema, sunburn, and chronic reactions, including premature skin aging and skin cancer. Aim, In this study, the effects of a topical antioxidant mixture consisting of vitamin C, ferulic acid, and phloretin on attenuating the harmful effects of UV irradiation on normal healthy volunteers were studied using biomarkers of skin damage. Subjects/methods, Ten subjects (age, 18,60 years; Fitzpatrick skin types II and III) were randomized and treated with antioxidant product or vehicle control on the lower back for four consecutive days. On day 3, the minimal erythema dose (MED) was determined for each subject at a different site on the back. On day 4, the two test sites received solar-simulated UV irradiation 1,5× MED at 1× MED intervals. On day 5, digital images were taken, and 4-mm punch biopsies were collected from the two 5× MED test sites and a control site from each subject for morphology and immunohistochemical studies. Results, UV irradiation significantly increased the erythema of human skin in a linear manner from 1× to 5× MED. As early as 24 h after exposure to 5× MEDs of UV irradiation, there were significant increases in sunburn cell formation, thymine dimer formation, matrix metalloproteinase-9 expression, and p53 protein expression. All these changes were attenuated by the antioxidant composition. UV irradiation also suppressed the amount of CD1a-expressing Langerhans cells, indicating immunosuppressive effects of a single 5× MED dose of UV irradiation. Pretreatment of skin with the antioxidant composition blocked this effect. Conclusion, This study confirms the protective role of a unique mixture of antioxidants containing vitamin C, ferulic acid, and phloretin on human skin from the harmful effects of UV irradiation. Phloretin, in addition to being a potent antioxidant, may stabilize and increase the skin availability of topically applied vitamin C and ferulic acid. We propose that antioxidant mixture will complement and synergize with sunscreens in providing photoprotection for human skin. [source] Langerhans cells in squamous cell carcinoma vs. pseudoepitheliomatous hyperplasia of the skinJOURNAL OF CUTANEOUS PATHOLOGY, Issue 12 2007Anjela Galan Background:, In clinical and histopathological practice, it is sometimes difficult to distinguish pseudoepitheliomatous hyperplasia (PEH) from squamous cell carcinoma (SCC) of the skin. Several studies have shown a low density of Langerhans cells in SCC of the skin, and recent research on cervical SCCs has suggested that the decreased density of dendritic cells is secondary to low E-cadherin expression. SCCs of the head and neck similarly have decreased E-cadherin expression, but E-cadherin expression is preserved in PEH. We hypothesized that PEH of the skin would have an increased number of Langerhans cells compared with SCC. Methods:, We studied immunohistochemical expression of CD1a on paraffin-embedded tissue in 12 cases of SCC and 11 cases of PEH of the skin. Results:, The number of Langerhans cells in SCCs vs. PEH was similar; in both types of lesions, the Langerhans cells were decreased in density compared with the normal flanking epidermis. Conclusions:, PEH has a decreased number of Langerhans cells compared with the normal epidermis. As SCCs also have decreased numbers of CD1a-positive cells, this stain is not useful in differentiating these two entities. [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] Identity of TUNEL-positive cells in the oral buccal epithelium of normal mucosa and lichen lesionsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2004Andreas Karatsaidis Background:,In situ detection of DNA fragmentation by TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick end labeling (TUNEL) is a widely used technique to identify apoptotic cells in the terminal phases of cell death. Several studies have shown that there are statistically increased numbers of TUNEL+ cells within the epithelium of oral lichen (OL). It was suggested that this indicates an increased rate of apoptosis among basal and suprabasal keratinocytes in OL epithelium. The aim of this study was to identify the TUNEL+ cells in the epithelium of erythematous (ERY) OL and normal oral mucosa (NOM). Methods:, Sections of biopsies from NOM and ERY OL were processed for TUNEL combined with immunostaining for pan-cytokeratin or for cell markers specifically expressed by different leukocytes. Results:, In NOM, TUNEL+ keratinocytes were almost exclusively seen in the outermost epithelial layers. This labeling was absent in ERY OL. In the basal and lower spinous layers, more TUNEL+ cell nuclei were seen in ERY OL as compared with NOM, in accordance with previous studies. The present observations show, however, that only very few of these cells were keratinocytes, but rather were CD4+ lymphocytes and CD68+ macrophages. There was no difference between the numbers of TUNEL+ keratinocytes in basal and lower spinous layers in ERY OL and NOM epithelium. No intraepithelial CD8+ lymphocytes, Langerhans cells, or mast cells were found to be TUNEL+. Conclusion:, The findings indicate that the pathologic changes in ERY OL epithelium cannot be explained by increased prevalence of terminal keratinocyte cell death identified by TUNEL. [source] Tetanus toxoid-loaded transfersomes for topical immunizationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2005Prem N. Gupta Topical immunization is a novel immunization strategy by which antigens and adjuvants are applied topically to intact skin to induce potent antibody and cell-mediated responses. Among various approaches for topical immunization, the vesicular approach is gaining wide attention. Proteineous antigen alone or in combination with conventional bioactive carriers could not penetrate through the intact skin. Hence, specially designed, deformable lipid vesicles called transfersomes were used in this study for the non-invasive delivery of tetanus toxoid (TT). Transfersomes were prepared and characterized for shape, size, entrapment efficiency and deformability index. Fluorescence microscopy was used to investigate the mechanism of vesicle penetration through the skin. The immune stimulating activity of these vesicles was studied by measuring the serum anti-tetanus toxoid IgG titre following topical immunization. The immune response was compared with the same dose of alum adsorbed tetanus toxoid (AATT) given intramuscularly, topically administered plain tetanus toxoid solution, and a physical mixture of tetanus toxoid and transfersomes again given topically. The results indicated that the optimal transfersomal formulation had a soya phosphatidylcholine and sodium deoxycholate ratio of 85:15%, w/w. This formulation showed maximum entrapment efficiency (87.34±3.81%) and deformability index (121.5±4.21). An in-vivo study revealed that topically administered tetanus toxoid-loaded transfersomes, after secondary immunization, elicited an immune response (anti-TT-IgG) comparable with that produced by intramuscular AATT. Fluorescence microscopy revealed the penetration of transfersomes through the skin to deliver the antigen to the immunocompetent Langerhans cells. [source] Murine and human Langerhans cells express a functional histamine H4 receptor: modulation of cell migration and functionALLERGY, Issue 7 2010M. Gschwandtner To cite this article: Gschwandtner M, Rossbach K, Dijkstra D, Bäumer W, Kietzmann M, Stark H, Werfel T, Gutzmer R. Murine and human Langerhans cells express a functional histamine H4 receptor: modulation of cell migration and function. Allergy 2010; 65: 840,849. Abstract Background:, Histamine is an important mediator of allergic reactions, and recent studies indicated that the function of different types of antigen presenting cells (APC) can be modulated by histamine, in particular via the newly described histamine H4 receptor (H4R). Therefore, we investigated possible interactions of histamine via the H4R on Langerhans cells (LC), which represent the professional APC in the skin and therefore have an important role in the initiation and maintenance of allergic skin diseases. Methods:, The expression of the H4R was evaluated by real-time PCR, flow cytometry and immunofluorescence staining. The function of the H4R was determined by intracellular flow cytometric measurement of chemokine production and LC migration assays. Results:, Here, we show H4R expression on in vitro generated monocyte-derived LC (mRNA and protein) and on primary LC from murine and human skin samples (protein). The immunofluorescence staining in murine and human skin samples clearly proved that LC express the H4R in situ. Stimulation with histamine or a H4R agonist downregulated the chemokine (C-C motif) ligand 2 (CCL2) in human monocyte-derived LC and primary LC. Prestimulation with a selective H4R antagonist abolished this effect. Moreover, migration of LC from the epidermis was increased after H4R agonist stimulation in ex vivo migration assays using human epidermis and murine in vivo assays. Conclusion:, Our findings show that LC express a functional H4R and point towards a possible pathogenic relevance of the H4R in inflammatory and allergic diseases. [source] | |||||||||||||||||||||||||||||||