Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An immunoelectron-microscopic technique was applied to investigate the localization of molecules that are involved in the elicitation of allergic contact dermatitis in human epidermal cells in situ. Langerhans cells in the epidermis of lesions showed a strongly increased cell surface expression of HLA class II molecules as compared with normal skin. In addition, a high number of intracellularly located HLA class II molecules were present in Langerhans cells of lesional epidermis, suggesting increased biosynthesis of these molecules during the elicitation process. In contrast, no differences in the expression of CD1a by Langerhans cells was observed between normal and lesional skin. Frequently, the Langerhans cells were found in close apposition to mononuclear cells, which also exhibited a strong cell surface HLA class II expression. The number of Birbeck granules that are characteristic intracellular Langerhans cells organelles was increased in lesional Langerhans cells as compared with normal-skin Langerhans cells, which may correlate with the activated state of lesional Langerhans cells. These Birbeck granules were always HLA class II or CD1a negative. The increased synthesis and expression of HLA class II molecules on the cell surface of Langerhans cells suggests a direct role for these HLA class II molecules in the elicitation process of allergic contact dermatitis.
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PMID:HLA class II expression on human epidermal Langerhans cells in situ: upregulation during the elicitation of allergic contact dermatitis. 142 38

INTRODUCTION. Atopic dermatitis (AD), allergic rhino-conjunctivities and allergic asthma constitute the classical triad of atopic diathesis attended, in many cases, by high serum IgE levels. While the pathophysiology of IgE-mediated allergic respiratory diseases is now better understood, the pathophysiological significance of atopic phenomena in the genesis and control of AD is still far from being clear. Numerous clinical and laboratory data point to a pathophysiological relation between IgE-mediated reactions and AD, but no one yet knows by which mechanism this interaction takes place. Some recent studies suggest that Langerhans cells might well be the missing link. THE LANGERHANS CELLS. Langerhans cells (LC) are dendritic epidermal cells originating in the bone marrow and supposedly belonging to the monocyte lineage. Their circulating precursors, the mechanism of their migration into the epidermis and their relationship with other dendritic cells, such as the interdigitating follicular cells, are controverted. LC express numerous surface markers, such as class I and II HLA, CD1a, CD4 and receptors for complement and IgE Fc fragments. Under normal conditions, LC do not express IgE receptors. Ultrastructurally, LC are characterized by the presence of Birbeck granules in their cytoplasm. Among the presumed functions of LC in the skin, the best documented is the presentation of antigens to T lymphocytes in allergic contact dermatitis. LANGERHANS CELLS IN ATOPIC DERMATITIS. Quantitative studies. Modern immunohistological methods based on the reactivity of monoclonal anti-CD1a antibodies have given results that are sometimes conflicting due to differences in the quantification techniques utilized. However, morphometric enumeration of LC on cryostat sections have shown that their number is about the same in AD and in normal skin. PRESENCE OF IgE BEARING LANGERHANS CELLS IN ATOPIC DERMATITIS. The presence of IgE molecules on the LC surface has been demonstrated in subjects with AD. It must be noted that in atopic subjects IgE bearing Lc are only found in patients with high serum IgE levels. They are absent in asthma patients without eczema, irrespective of their serum IgE levels. Daily applications of corticosteroids on AD lesions result in a decrease of anti-IgE markers on LC after one week and in their complete disappearance after 2 weeks. IN ATOPIC DERMATITIS LANGERHANS CELLS EXPRESS A RECEPTOR SPECIFIC TO Fc FRAGMENTS OF IgE. The exact nature of the receptor for IgE expressed in situ in AD patients is still conjectural. Some authors have been able to demonstrate that the binding of IgE molecules by LC isolated from the skin of atopic patients is inhibited by a monoclonal antibody directed against the low affinity receptor (Fc epsilon R2) of eosinophils and macrophages. This strongly suggests that certain factors induce the expression by LC of an Fc epsilon R2 receptor. IN VITRO INDUCTION OF IgE RECEPTORS ON NORMAL LANGERHANS CELLS...
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PMID:[Langerhans cells in the physiopathology of atopic dermatitis]. 219 89

We have investigated the mechanisms by which topical corticosteroids modulate cutaneous immune reactions in man. Volunteers applied clobetasone butyrate 0.05% (Eumovate; EV), betamethasone valerate 0.1% (Betnovate; BV), clobetasol propionate 0.05% (Dermovate; DV), and control vehicles twice daily to forearm skin for 7 days. Steroid therapy significantly decreased the number of HLA-DR/T6 (CD1a) positive Langerhans cells (LCs) per mm2 in suction blister-derived epidermal sheets, expressed as a mean percentage of controls, as follows: EV 69.2%; BV 67.3%; DV 37.8%. LC antigen presenting capacity was determined in the allogeneic and autologous epidermal cell-lymphocyte reactions. The LC-dependent allostimulatory capacity of epidermal cells, expressed as a mean percentage of controls, was also significantly reduced by steroid therapy: EV 45.1%; BV 41.9%; DV 23.4%. Following therapy with clobetasol propionate 0.05%, the capacity of epidermal cells to present tetanus toxoid to, and to augment concanavalin A mediated lymphocyte stimulation of, autologous lymphocytes was reduced to 33.6% and 19.7% respectively of controls. Depression of epidermal cell allostimulatory capacity was not the result of a steroid-induced decrease in the production of epidermal cell-derived thymocyte activating factor (ETAF)/interleukin 1 by keratinocytes, since it could not be reversed by addition of exogenous interleukin 1. Indomethacin, added to block any potential prostaglandin synthesis during the culture period, did not restore the allostimulatory capacity of epidermal cells from steroid-treated sites. Addition of epidermal cells from DV-treated sites depressed the capacity of control epidermal cells to stimulate lymphocytes in the allogeneic epidermal-lymphocyte reaction. Our results demonstrate that the anti-inflammatory action of topical corticosteroids in man is associated not only with a reduction in the number of HLA-DR/T6 positive LCs, but also with a marked decrease in Langerhans cell-dependent T lymphocyte activation. The effects of the different steroids on both of these parameters correlated with their potency as determined in the standard occlusive vasoconstrictor assay. Topical corticosteroids are widely used for the treatment of inflammatory skin disorders, and inhibit not only the elicitation phase, but also the induction phase, of allergic contact dermatitis reactions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of topical corticosteroid therapy on Langerhans cell antigen presenting function in human skin. 328 68

Interactions of CD28 (on T cells) with its recently identified ligand B7/BB1 (on antigen-presenting cells) have been shown to activate T cells via a major histocompatibility complex/Ag-independent "alternative" pathway, leading to an amplification of T-cell-mediated immune responses. The in vivo relevance of these molecules for cutaneous immunity is presently unknown. These findings prompted us to study the expression of B7/BB1 and CD28 in normal human skin and in selected T-cell-mediated inflammatory skin diseases. Biopsies were obtained from lesional skin of patients with allergic contact dermatitis, lichen planus, and, as control, from basal cell carcinoma and from healthy controls. Serial cryostat sections were stained with a panel of MoAbs directed against CD28, B7/BB1, CD3, CD1a, and KiM8 using immunohistochemistry (ABC technique). CD28 expression was observed in the majority of dermal and epidermal CD3+ T cells in contact dermatitis and lichen planus. In normal skin and basal cell carcinoma, CD28 was expressed only occasionally by perivascular T cells. In allergic contact dermatitis and lichen planus, B7/BB1-expression was found on dermal dendritic cells, on dermal macrophages, on Langerhans cells, focally on keratinocytes, and occasionally on dermal T cells. No B7/BB1 immunoreactivity was detected in normal skin and basal cell carcinoma. These findings indicate that T-cell-mediated skin diseases are accompanied by an influx of CD28+ T cells and an upregulation of B7/BB1 on cutaneous antigen-presenting cells, keratinocytes, and on some T cells. We speculate that "alternative" T cell-activation via the B7/CD28 pathway may contribute to the pathogenesis of these skin diseases.
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PMID:Expression of the B7/BB1 activation antigen and its ligand CD28 in T-cell-mediated skin diseases. 752 32

The family of protein kinase C (PKC) isoenzymes plays a fundamental part in signal transduction, and thereby regulates important cellular functions, including growth, differentiation, cytokine production and adhesion molecule expression. In lesional psoriatic skin, Ca(2+)-dependent PKC activity, PKC-beta protein and epidermal Langerhans cell (LC) PKC-beta immunostaining are significantly decreased, indicating activation and subsequent down-regulation of PKC. Whether these changes occur in other inflammatory/hyperplastic dermatoses is, however, unknown. We examined PKC-alpha and PKC-beta expression in normal skin, psoriasis, cutaneous T-cell lymphoma (CTCL), lamellar ichthyosis, non-bullous ichthyosiform erythroderma, atopic dermatitis, urushiol-induced allergic contact dermatitis, and sodium lauryl sulphate (SLS)-induced irritant contact dermatitis. Cryostat sections were stained for PKC-alpha and PKC-beta, and the LC marker CD1a, using an immunoperoxidase technique and specific monoclonal antibodies. Double-labelling studies, in normal skin, revealed co-expression of PKC-beta and CD1a by epidermal LCs. Analysis of the number of PKC-beta+ and CD1a+ epidermal LCs, in diseased compared with normal skin, revealed three categories: (i) in psoriasis and CTCL, the PKC-beta+ epidermal LC number was significantly reduced, whereas the CD1a+ epidermal LC number was unchanged; (ii) in allergic and irritant contact dermatitis, both PKC-beta+ and CD1a+ epidermal LCs were significantly reduced in number; and (iii) in atopic dermatitis, the PKC-beta+ epidermal LC number was normal, and CD1a+ epidermal LCs were significantly increased in number. Moreover, the ratio of epidermal LC PKC+/CD1a+ was reduced in all the dermatoses studied, suggesting activation of PKC-beta, with subsequent down-regulation. Within the dermis, increased PKC-beta staining of infiltrating cells was observed in all the conditions studied except lamellar ichthyosis and non-bullous ichthyosiform erythroderma. These data indicate that: (i) down-regulation of LC PKC-beta occurs in a variety of inflammatory and hyperplastic skin disorders, and is not unique to psoriasis, and (ii) the pattern of epidermal LC PKC-beta and CD1a expression varies among the diseases studied. In mice, PKC activation induces LC migration. Thus, down-regulation of epidermal LC PKC-beta associated with reduced CD1a+ epidermal LCs in allergic and irritant contact dermatitis suggests that PKC-beta may transduce the signal for migration of LCs from human epidermis.
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PMID:Down-regulation of Langerhans cell protein kinase C-beta isoenzyme expression in inflammatory and hyperplastic dermatoses. 754 80

By means of microsurgical lymph cannulation human skin lymph derived from the late phase of an elicitation reaction to diphenylcyclopropenone was sampled. Cells were isolated by centrifugation and then treated with mouse anti-CD1a monoclonal antibodies and sheep antimouse antibody-coated Dynabeads. Ultrastructural and immunocytochemical analyses revealed anti-CD1a/Dynabead-rosetted CD1a- and protein S-100-positive cells which did not express monocyte surface markers, but surface antigens such as HLA-DR, ICAM-1 and, in part, LFA-3. In comparison to freshly prepared human epidermal Langerhans cells (LC), a large fraction of these cells contained no or markedly fewer Birbeck granules and exhibited extensive ruffling of the surface. These data suggest that the phenotype of LC in skin lymph derived from the elicitation phase of allergic contact dermatitis is similar to LC cultured in vitro. In the functional concept of LC of our time, these cells correspond to the dendritic cells designated as "veiled".
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PMID:Phenotype of Langerhans cells in human afferent skin lymph derived from allergic contact dermatitis. 816 48

In order to monitor the kinetics of Langerhans cells in the afferent lymph during contact dermatitis, a superficial peripheral lymph vessel draining the skin of the upper and medial part of the foot was cannulated by means of microsurgery on the lower leg of four healthy volunteers. After 2 days an irritant contact dermatitis was induced by application of 10% sodium lauryl sulphate to the area of skin drained by the cannulated lymph vessel. Three days later the spontaneously regressing skin reaction was treated with clobetasol propionate in two of the subjects. Lymph was collected twice daily for 8 days. Langerhans cells were identified by immunofluorescence microscopy of cytocentrifuge slide preparations from the lymph, using a monoclonal anti-CD1a antibody. In the late phase of the contact dermatitis the output, i.e. both the absolute number and the percentage of Langerhans cells in the lymph dramatically increased. At the end of the experiment, when there were no remaining clinical signs of contact dermatitis, the Langerhans cell output still markedly exceeded the initial values. These results are the first direct evidence in humans that migration of Langerhans cells from the skin to the regional lymph nodes is a major feature of irritant contact dermatitis.
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PMID:Large increase of Langerhans cells in human skin lymph derived from irritant contact dermatitis. 845 53

Intercellular adhesion molecule (ICAM)-3 is a recently described member of the immunoglobulin superfamily and, as such, is closely related to ICAM-1 and ICAM-2. All three ICAMS are cognate for the counter-receptor lymphocyte function associated antigen-1 (LFA-1, CD11a/CD18). Unlike ICAM-1 and ICAM-2, ICAM-3 is constitutively expressed at high levels on resting leucocytes. We investigated the expression and function of ICAM-3 in normal skin (n = 5), as well as its expression in psoriasis (n = 4), atopic eczema (n = 4), allergic (rhus) contact dermatitis (n = 3), and cutaneous T-cell lymphoma (CTCL, n = 2). Five-micrometre cryostat sections of skin were stained using monoclonal antibodies to ICAM-3 and a well characterized immunoperoxidase technique. In normal skin, ICAM-3 was expressed by all cutaneous leucocytes but most striking was the strong expression of ICAM-3 by Langerhans cells within both epidermis and dermis. This observation was confirmed by double-labelling with CD1a and negative staining with an IgG1 isotype control. In psoriasis, atopic eczema, allergic contact dermatitis, and CTCL, ICAM-3 was co-expressed on all CD1a+ cells, although, in psoriasis, the intensity of ICAM-3 expression was reduced. Functional blocking experiments were performed to determine whether the observed ICAM-3 expression on Langerhans cells was functionally important in antigen presentation. CD4+ T cells were prepared from peripheral blood and 10(5) CD4+ T cells combined with 10(5) epidermal cells harvested from keratome biopsies of normal skin of an individual allogeneic to the T-cell donor. Addition of 50 micrograms anti-ICAM-3 to the co-culture resulted in a consistent (50%) reduction in degree of alloantigen presentation by Langerhans cells to T cells. Inhibition was 77% of that produced by the addition of anti-LFA-1. These data indicate that ICAM-3 is constitutively expressed by Langerhans cells and is a major ligand for LFA-1 on CD4+ T cells during their response to Langerhans cells. Because fresh Langerhans cells constitutively express little ICAM-1, whereas ICAM-3 is constitutively expressed at high levels, it would appear that ICAM-3 is the dominant functional ICAM on in situ Langerhans cells in the normal epidermis.
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PMID:The ICAM-3/LFA-1 interaction is critical for epidermal Langerhans cell alloantigen presentation to CD4+ T cells. 854 30

Immunological mechanisms play an important role in the pathogenesis of psoriasis. Lesional psoriatic skin-derived T-cell clones have been shown to stimulate keratinocyte proliferation and to predominantly express a T-helper type 1 cytokine pattern. However, T-helper type 2-like cytokines have also been identified in some psoriatic T-cell clones. In parallel to the T-helper type 1/type 2 dichotomy, a distinction between interferon-gamma-induced (classically activated) macrophages and interleukin-4/glucocorticoid-induced (alternatively activated) macrophages has been put forward as a conceptual framework for a better understanding of immunopathological processes. In the present study, the phenotype of mononuclear phagocytes in psoriatic skin lesions (n = 21), allergic contact dermatitis (n = 4) and normal skin (n = 2) was investigated using a panel of monoclonal antibodies (mAb) against monocytes/macrophages and dendritic cells (mAb MS-1, RM 3/1, and 25F9 against subsets of in vitro alternatively activated macrophages, and mAb against myeloid antigens CD1a, CD11b, CD11c, CD34, CD36, and CD68). With regard to mononuclear phagocytes, psoriatic skin was found to be compartmentalized into epidermis, subepidermal space, and upper and lower dermis. RM 3/1++ +, MS-1+/-, 25F9- dendritic macrophages previously classified as type II alternatively activated macrophages were the dominant dermal macrophage population in psoriatic skin, while intraepidermal and epithelium-lining macrophages expressed a different, presumably classically activated, macrophage phenotype (RM 3/1-, MS-1-, 25F9-, CD68+2, CD11b+2). In allergic contact dermatitis, a classical T-helper type 1 disease, RM 3/1++ + macrophages were less prominent. Since MS-1 high molecular weight protein is much more sensitive to interferon-gamma-induced suppression than RM 3/1 antigen, a predominance of T-helper type 1 cytokines in psoriasis could explain why dermal dendritic macrophages do not express the fully induced MS-1++ +, RM 3/1++ +, 25F9+/- phenotype of type I alternatively activated macrophages.
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PMID:Immunohistochemical identification of type II alternatively activated dendritic macrophages (RM 3/1+3, MS-1+/-, 25F9-) in psoriatic dermis. 895 Apr 56

Previously, we have showed that artificial epidermal permeability barrier disruption leads to an increase in epidermal Langerhans' cell (LC) density within 24 h. We now asked if this is accompanied by an enhancement of allergic contact dermatitis. Barrier disruption was induced by acetone on the upper arms in 6 volunteers with known sensitization to nickel, fragrance mix, or p-phenylenediamine. Twenty-four hours after this treatment the relevant allergen was applied without occlusion or with Finn chambers. Twenty-four hours after application of the allergen, clinical grading and transepidermal water loss (TEWL) measurements were performed and biopsies were taken. Immunohistochemical stainings for LCs (anti-CD1a, Leu6) and for epidermal proliferation (Ki-S3) were performed. Open applications of the allergens after acetone pretreatment resulted in strong allergic test reactions. TEWL, which showed a 70% recovery 24 h after acetone treatment, was increased again 4-fold by the allergic test reactions. LC density, which was increased by 80% 24 h after acetone-induced barrier disruption, was further enhanced 2.4-fold in total. Epidermal proliferation showed a 6-fold increase after open application of the allergens. Under patch test conditions after acetone pretreatment very strong bullous reactions were observed. We conclude that the increase in epidermal LC density induced by epidermal permeability barrier disruption is accompanied by an enhanced response in allergic contact dermatitis.
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PMID:Influence of epidermal permeability barrier disruption and Langerhans' cell density on allergic contact dermatitis. 911 17


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