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

Although dithranol has been used for 75 years in the treatment of psoriasis, its working mechanism is still not resolved. In order to further define the mode of action of dithranol, the interference with normal skin was studied. The effect of dithranol on epidermal proliferation, keratinization and inflammation was examined using immunohistochemistry. Punch biopsies from 6 volunteers who applied dithranol 0.5% in petrolatum were taken before application, after 48 and 96 h. Biopsies were processed for assessing epidermal proliferation by Ki67 binding (cycling cells), for keratinization by Ks8.12 binding (keratin 13 and 16, keratin 16 is expressed by hyperproliferative keratinocytes) and RKSE60 binding (keratin 10). For assessing inflammation the antibodies antielastase (polymorphonuclear leukocytes (PMN)), T11 (T lymphocytes, CD2), T6 (Langerhans cells, CD1a) and WT14 (monocytes/macrophages, CD14) were used. Ki-67 staining started to increase between 48 and 96 h whereas Ks8.12 binding had increased already between 0 and 48 h. RKSE60 staining showed a decline between 48 and 96 h. Inflammation in the dermis showed an increase after 48 h, and continued to increase. In the inflammatory infiltrate, the accumulation of PMN was limited compared to the pronounced infiltration of T lymphocytes. Langerhans cell shape and epidermal position altered in 4 volunteers. Application of dithranol on normal skin produces analogies and discrepancies compared to application of dithranol on psoriatic lesions. Direct interference with epidermal growth and differentiation seems less likely as the antipsoriatic principle.
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PMID:Topical application of dithranol on normal skin induces epidermal hyperproliferation and increased Ks8.12 binding. 137 64

CD36 recognizes a 88 Kd glycoprotein, found on different cell populations involved in immunoregulation and are induced on keratinocytes by in vitro treatment with gamma-interferon. Therefore, we obtained skin biopsies from 48 patients with various dermatological diseases and from 5 healthy volunteers and stained these with monoclonal antibodies OKM5 (CD36), anti-HLA-DR and OKT6 (CD1a) using a three stage immunoperoxidase method. In normal skin, CD36 expression was not observed. In contrast, keratinocytes in diseased skin were CD36+. In most cases, the staining was restricted to the stratum granulosum and the stratum spinosum, but in psoriasis, squamous cell carcinoma and lymphomatoid papulosis, more extensive staining of keratinocytes was seen. In addition, CD36+ epidermal leukocytes were found in allergic patch-test infiltrates and in mycosis fungoides. The findings of CD36 expression by epidermal cells within a broad spectrum of dermatological diseases indicate a role for these cells in the regulation of immune reactions in the skin.
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PMID:Keratinocyte and epidermal leukocyte expression of CD36 (OKM5) in benign and malignant skin diseases. 168 91

The objective of this study was to determine whether epidermal cells (EC) from psoriasis lesions and uninvolved skin could stimulate autologous T lymphocytes in the in vitro autologous mixed epidermal cell-T lymphocyte reaction (autologous MECLR). The functional role of antigen-presenting cell (APC) subsets was concurrently determined in this reaction. Mononuclear cells and purified T lymphocytes from peripheral blood of psoriasis patients showed a clear proliferative response to autologous unpurified epidermal cells from involved as well as uninvolved skin. The autologous mixed leukocyte reaction (MLR) was not elevated in psoriasis patients. In healthy controls and contact allergy patients, T-lymphocyte proliferation was not observed either in the autologous MECLR or in the autologous MLR. The level of proliferation in the autologous MECLR from psoriasis patients correlated to the number of epidermal cells that were added. To exclude the possibility that the observed proliferation in the autologous MECLR in psoriasis was due to the presence of epidermal T lymphocytes that were being stimulated and expanded in vitro, the stimulator EC were gamma irradiated (30 Gy) in some experiments. Preincubation of EC with cyclosporin A (CsA) significantly inhibited the autologous MECLR. The CsA-induced inhibition could be neutralized by the addition of fresh untreated EC to these cultures. This indicated that one of the modes of action of CsA in resolving psoriasis is, as some investigators have already shown, via inhibition of epidermal accessory cell function. In the autologous MECLR, APC from psoriasis skin could initiate this reaction, whereas APC from peripheral blood could not. This occurred in an MHC class II restricted fashion. Depletion experiments showed that Langerhans cells (HLA-DR+/CD1a+) were not the principal stimulators of autologous T lymphocytes in the MECLR. These results indicated that mainly HLA-DR+/CD1a- epidermal cells from psoriasis patients could stimulate autologous peripheral blood T lymphocytes in an MHC class II-restricted fashion.
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PMID:The autologous mixed epidermal cell-T lymphocyte reaction is elevated in psoriasis: a crucial role for epidermal HLA-DR+/CD1a- antigen-presenting cells. 171 Jun 38

Cyclosporin A, a potent immunosuppressive drug currently used in organ transplant recipients, has been shown to exert in vitro a direct antiproliferative effect on a number of cell types present in the skin, including keratinocytes, fibroblasts, and endothelial cells. Although in vitro studies suggest that cyclosporin A may interfere with the functional capacities of epidermal Langerhans cells, there is no evidence that the treatment influences the distribution or number of Langerhans cells in vivo. We used a model of normal human skin graft to "nude" mice, which is free of the human systemic control mechanisms, for studies on the DNA synthesis of human Langerhans cells under the influence of cyclosporin A. The grafted animals were given daily subcutaneous (50 mg/kg) or intraperitoneal (5, 12.5, and 25 mg/kg) drug injections during three weeks, which resulted in mean blood levels comparable to those observed in treated patients with organ transplants or psoriasis, respectively. BrdU administered during the last week of the experiment was incorporated by all cells synthesizing DNA, including those passing through S-phase. Langerhans cells were detected on deparaffinized or frozen tissue sections of xenografts with anti-CD1a and anti-HLA DR monoclonal antibodies, and the number of BrdU-positive cells was determined by double labeling. Our results indicate that the Langerhans cell DNA synthesis is impaired by therapeutic levels of cyclosporin A.
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PMID:Cyclosporin A inhibits DNA synthesis by epidermal Langerhans cells. 171 49

Epidermal dendritic and T-cell counts have been performed in lesional and non-lesional skin from 35 psoriatic patients. The aims were to investigate absolute changes and interrelationships between these cellular elements in psoriasis and to explain apparent discrepancies between these results and reports in the literature. In non-lesional skin, the most frequently expressed dendritic cell marker was CD1a. HLA-DR+ and alpha-mannosidase+ dendritic cells were approximately 50 per cent and S100+ cells were 25 per cent as frequent. T-lymphocytes were rare, CD4+ cells predominating. In lesional psoriatic epidermis, there was a definite increase (approximately two-fold) in the absolute number of CD1a+ dendritic cells. This differs from the conclusions from the majority of previous studies. However, when cell counts were expressed per unit area of vertical section, there was a decrease in CD1a+ cells in lesional skin, which is an explanation for this discrepancy. There was a greater increase in absolute HLA-DR+ cell counts, so that the numbers of cells expressing CD1a and HLA-DR were similar in lesional skin. S100 expression increased proportionately with CD1a+, but there was no absolute increase in alpha-mannosidase+ cells, which might represent a separate sub-population of dendritic cells. The greatest cellular increase was in T-lymphocytes, particularly CD8+. In lesional skin, direct correlations have been demonstrated between epidermal thickness, HLA-DR+ dendritic cells and T-lymphocytes, particularly CD8+ cells. We would suggest that the present method of quantification is of value for the analysis of absolute changes in epidermal infiltrates, particularly psoriasis, and could be applied to other epidermal pathologies.
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PMID:Assessment of epidermal dendritic cell markers and T-lymphocytes in psoriasis. 752 11

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

The papillary dermis of psoriasis and mycosis fungoides (MF) lesions is characterized by prominent collections of cells with dendritic morphology. Immunophenotypically distinct populations of cutaneous dendritic cells have been identified as CD1a+, FXIIIa-Langerhans cells (LC) and CD1a-, FXIIIa+ dermal dendritic cells (DDC). In this study, antibodies against the human CD1 cluster of antigens (i.e. CD1a, CD1b and CD1c) and the DDC marker (FXIIIa) were used to further characterize the subsets of dendritic cells in normal skin as compared to neonatal foreskin, psoriasis and MF by both immunoperoxidase and double immunofluorescence techniques. Normal skin and foreskin epidermis and dermis contained few CD1b+ or CD1c+ cells along with normal numbers of CD1a+ LC and FXIIIa+ DDC. Both MF and psoriasis were characterized by CD1a+ cells in the epidermis and dermis. FXIIIa+ cells were greatly expanded in the upper dermis of MF lesions and to a lesser degree in psoriasis as has been previously described by our group. MF contained significantly increased epidermal and dermal CD1b+ (15.7/5 high power fields [HPF] and 59.7/5 HPF respectively) and CD1c+ dendritic cells (33.8/5 HPF and 95.9/5 HPF respectively), while in psoriasis these cells were not statistically different from normal skin. Double immunofluorescence studies revealed that some (< 25%) FXIIIa+ cells co-expressed CD1b and CD1c in MF > psoriasis > foreskin, while FXIIIa+ DDC never co-expressed CD1a. Thus, in contrast to normal skin in which epidermal or dermal dendritic cells rarely express CD1b and CD1c antigens, these members of the CD1 family are upregulated on both LC and DDC in benign and malignant inflammatory states.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distinctive dendritic cell subsets expressing factor XIIIa, CD1a, CD1b and CD1c in mycosis fungoides and psoriasis. 759 15

In conclusion we have shown that motile cells with a dendritic morphology can be isolated from dermis of normal and diseased human skin. DDC bear high amounts of MHC class II molecules on their surface, and are very potent antigen presenting cells. Subpopulations of these cells acquire certain ultrastructural features of Langerhans cells in-vitro such as Birbeck granule formation and CD1a expression. These newly defined members of the dendritic cell family of APCs may be precursors of epidermal Langerhans cells and may play a role in skin immune responses. Furthermore in inflammatory dermatoses such as psoriasis, a role in the autostimulation and cytokine production of T cells could be demonstrated. Given their number, distribution, and in-vitro functional capacity, it is appropriate at this time to conclude that DDCs are indeed important members of the skin immune system.
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PMID:Dermal dendritic cells are important members of the skin immune system. 852 32

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

The roles of sialyl-Lewisx antigen were evaluated in the pathogenesis of psoriasis. Sialyl-Lewisx expression was investigated immunohistochemically in the epidermis of normal human skin and erythematous lesional skin of psoriasis vulgaris by avidin-biotin-peroxidase complex procedures. A few sialyl-Lewisx positive dendritic cells were detected in the epidermis of normal human skin. In 7 out of 9 cases of psoriasis vulgaris, the number of sialyl-Lewisx-positive epidermal dendritic cells increased in the erythematous lesion over the adjacent normal skin; there were no marked changes in the numbers of CD1a-positive cells in the epidermis between the two skin types. In the double immunofluorescence studies, more than half of the sialyl-Lewisx-positive epidermal cells in psoriatic erythema were stained with a monoclonal Lag antibody that specifically reacts with Birbeck granules and related structures of human Langerhans cells. Furthermore, we determined the changes in serum levels of sialyl-Lewisx antigens in patients with psoriasis. Although levels in the sera were not significantly elevated over those of controls, the increases correlated with the degree of disease activity. These findings suggest that sialyl-Lewisx antigen is possibly involved in the development of psoriasis.
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PMID:Evaluation of sialyl Lewisx antigen in the skin and the sera of patients with psoriasis vulgaris. 883 35


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