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)

Atopic dermatitis is a disorder characterized by cutaneous exanthemata as a consequence of exaggerated eczematous reactions to topical and systemic allergens. Langerhans cells, expressing CD1a and HLA-DR, and dermal dendritic cells, expressing HLA-DR, are known to be potent antigen-presenting cells and are thought to play an important role in the pathogenesis of atopic dermatitis. The immunophenotype of lesional skin in atopic dermatitis in humans involves increased numbers of CD1a+/MHC class II+ dendritic cells in addition to activated T cells, mast cells, and macrophages. To establish feline skin as a model for the study of human atopic dermatitis, and to elucidate the role of dendritic cells in feline atopic dermatitis, we investigated the presence of CD1a+ cells and MHC class II+ cells in the epidermis and dermis of lesional feline skin and in skin of healthy control animals. Immunohistochemistry revealed that MHC class II+ epidermal dendritic cells were CD1a+ in normal feline skin and significantly increased numbers of CD1a+ cells and MHC class II+ cells were present in the epidermis and dermis of lesional skin. These data provide the first correlative documentation of CD1a expression by feline dendritic cells containing Birbeck granules, and indicate the utility of feline skin in the study of human cutaneous atopy.
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PMID:Feline atopic dermatitis. A model for Langerhans cell participation in disease pathogenesis. 932 25

In this study, we investigated the effect of ultraviolet B radiation on human Langerhans cell function. Normal human skin was irradiated ex vivo with single doses of ultraviolet B. For assessment of T-cell stimulatory function, cells that spontaneously migrated from epidermal sheets were used, whereas full-thickness skin biopsies were used to investigate alterations in migratory properties. The cells migrating from ultraviolet B-exposed epidermal sheets demonstrated a decrease in the percentage of HLA-DR positive Langerhans cells, as well as a reduced capacity to induce proliferation of allogeneic T cells, when compared with cells migrating from nonexposed sheets. When a correction was made for the decreased number of HLA-DR positive Langerhans cells migrating from ultraviolet B-exposed epidermis, however, it appeared that the capacity to induce T-cell proliferation was identical for Langerhans cells migrating from ultraviolet B-exposed and nonexposed epidermis. The presence of ultraviolet B-induced DNA damage could be demonstrated in the Langerhans cells from ultraviolet B-treated skin, indicating that the cells had received significant doses of ultraviolet B. As regards the effect of ultraviolet B on migratory properties of Langerhans cells, we found not only that reduced numbers of CD1a-positive Langerhans cells migrated from the ultraviolet B-exposed full-thickness skin, but also that there was a reduction in CD1a-positive Langerhans cells in the epidermis. This implies that ultraviolet B induces death of Langerhans cells as well as loss of cell surface molecules rather than altering Langerhans cells migration, whereas the Langerhans cells that were still able to migrate fully retained the capacity to activate allogeneic T cells.
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PMID:Despite the presence of UVB-induced DNA damage, HLA-DR+ cells from ex vivo UVB-exposed human skin are able to migrate and show no impaired allostimulatory capacity. 934 89

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1+ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a+ cells and a moderate increase of HLA-DR+ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1+ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.
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PMID:Effect of UVB 311 nm irradiation on normal human skin. 937 27

We report the generation of dendritic cells (DC) starting from CD34+ bone marrow (BM) progenitor cells, using a two-stage culture system in which, besides granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-alpha), stem-cell factor (SCF) was added during the first 5 days, while interleukin-4 (IL-4) and/or interferon-gamma (IFN-gamma) were added during the secondary culture period of 9 days. Addition of IL-4 favoured the outgrowth of CD1a+, HLA-DR+, CD4+, CD40+, CD80+ but CD14- cells with dendritic morphology and strong antigen-presenting capacity. Addition of IFN-gamma selectively induced HLA-DR and CD86 but did not up-regulate CD1a expression or antigen-presenting capacity of the differentiated cells. An antagonism between IL-4 and IFN-gamma could further be confirmed in that, as compared with IL-4 alone, the simultaneous addition of IL-4 and IFN-gamma to GM-CSF plus TNF-alpha during maturation reduced both the phenotypical (CD1a, CD4, CD40) and functional characteristics of DC. Using receptor-specific TNF-alpha mutants, we investigated the relative involvement of TNF-alpha receptors R1 and R2 in the generation of DC. The induction of CD1a and HLA-DR, as well as the increase in allostimulatory capacity were dependent on TNF-R1 triggering, whereas triggering through TNF-R2 had no measurable effect. We conclude first, that the expansion of DC from BM progenitors could most effectively be enhanced in a two-stage culture assay using SCF, GM-CSF, TNF-alpha and IL-4; second, that the effect of TNF-alpha in DC generation involves signalling via the TNF-R1 receptor; and third, that IFN-gamma counteracts some of the effects of IL-4 in DC generation.
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PMID:Generation of dendritic cells from bone marrow progenitors using GM-CSF, TNF-alpha, and additional cytokines: antagonistic effects of IL-4 and IFN-gamma and selective involvement of TNF-alpha receptor-1. 937 94

Dendritic cells (DCs), which are antigen presenting cells of potential use in human antitumor vaccination trials, are presently the subject of intense investigation. Many recent studies have reported the possibility of generating ex vivo large numbers of DCs with high antigen presenting capacity by the culture of bone marrow or blood progenitors. In this study, we examined the differentiation into DCs of CD34+ progenitors isolated from the G-CSF mobilized blood of 3 healthy donors and 5 patients with breast cancer and cultured in the presence of GM-CSF + IL-13. The characteristics of the cells were compared to those of cells obtained in the presence of GM-CSF + TNF alpha. By day 15, one third of the bulk cells cultured with IL-13 were CD1a+/CD14- and strongly expressed CD1c, CD40, CD80 and HLA-DR. In contrast, cells obtained with TNF alpha expressed CD1a on one in three cells but with a considerably lower fluorescence intensity than on IL-13-cultured cells and strongly expressed CD14 on more than 50% of cells. CD1a+/CD14- cells emerged in IL-13 cultures at day 5, while in TNF alpha cultures CD14+ cells appeared before CD1a+ cells. Cells grown in the presence of IL-13 had an increased capacity to present antigens to autologous lymphocytes and to stimulate allogeneic T-lymphocytes. This effect was greater than that of cells grown in the presence of TNF alpha. These cells should therefore have greater effector potential in any therapeutic applications in humans.
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PMID:IL-13 induces CD34+ cells isolated from G-CSF mobilized blood to differentiate in vitro into potent antigen presenting cells. 943 67

Excessive exposure to sunlight results in drastic degradative changes in the constitutive cells of the epidermis. Among these is a profound abrogation of Langerhans cell number and function, leading to compromised immunologic competency. Retinoids have recently been shown to restore immunologic function in the setting of iatrogenic immunosuppresion. We asked whether topical tretinoin would reverse Langerhans cell depletion in chronically photodamaged skin. We examined the skin of 8 volunteers immunohistochemically before and after 6 months of daily applications of tretinoin. At baseline, there was a profound depletion of CD1a-positive Langerhans cells in the interfollicular epidermis, but not in the adjoining follicular epithelium. After tretinoin, all patients demonstrated replenishment of interfollicular epidermis by CD1a-positive Langerhans cells. This was associated with induction of HLA-DR expression on infundibular keratinocytes, as well as the appearance of CD1a dendritic cells in the papillary dermis. Thus, the enhancement of epidermal immunity in photodamaged skin may reflect restoration of antigen-presenting Langerhans cells. The source of this renewed dendritic cell population is likely to be follicular infundibulum and the papillary dermis.
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PMID:Topical tretinoin replenishes CD1a-positive epidermal Langerhans cells in chronically photodamaged human skin. 950 41

Dermatofibroma is composed largely of interlacing fascicles of slender spindle cells set within a loose collagenous stroma and of scattered foamy histiocytes and multinucleated giant cells. There is clear evidence indicating that factor XIIIa+ dermal dendritic cells (DDCs) are the cells constituting dermatofibromas. However, it is still unknown what stimulation is responsible for transforming DDCs into different cell types, producing different subtypes of dermatofibromas. Recently, it has become possible to obtain dendritic cells (DCs), that are identical with DDCs in their phenotypic and functional characteristics, from the culture of CD14+ peripheral blood monocytes to which IL-4 and GM-CSF were added. Using these monocyte-derived DCs, we examined the ability of various cytokines, such as IL-1beta , IL-3, IL-5, IL-6, IL-7, IL-8, IL-10, TNFalpha, TGFbeta, M-CSF, IFNalpha, and IFNgamma, and phorbol 12-myristate 13-acetate (PMA), to induce different cell types observed in DFs. Among them, only PMA could induce a variety of cell types such as histiocytic cells, fibroblastic spindle-shaped cells, and even multinucleated giant cells of Touton or foreign body type. Phenotypically, all the induced cell types expressed CD1a, CD80, CD86, HLA-DR, and CD68 in a magnitude similar to that of non-treated monocyte-derived DCs. The expression of factor XIIIa was strongest in histiocytic cells, moderate in fibroblastic cells, and weakest or negative in giant cells. These data suggest that dermatofibromas are a kind of neoplastic disease which is induced only by the effect of some tumor promoter on DDCs.
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PMID:Phorbol 12-myristate 13-acetate can transform monocyte-derived dendritic cells to different cell types similar to those found in dermatofibroma. A possible in vitro model of the histogenesis of dermatofibroma. 952 94

Calcipotriene is a synthetic analogue of 1,25-dihydroxyvitamin D3 established to be effective topically in the treatment of psoriasis. We investigated the early cellular and immunological events induced by calcipotriene in psoriasis. Thirty patients with moderate plaque-type psoriasis were randomly assigned to receive twice daily applications of either calcipotriene ointment 0.005% or matching vehicle for 6 weeks. Skin biopsies (6 mm) were performed from designated plaques at baseline and days 3 and 7. On these days and at weeks 2, 4 and 6, complete clinical evaluations were made in a double-blind fashion. Consistent with previous studies, significant clinical improvement (P < 0.05) in psoriasis was observed in patients receiving calcipotriene vs. those receiving vehicle by day 7 for scale and erythema, and by day 14 for thickness. No significant improvement, however, was seen on day 3. None of the immunohistological markers (CD1a, CD4, CD8, ICAM-1, VCAM-1, E-selectin, HLA-DR) semiquantitatively assessed in psoriatic plaques was significantly changed by calcipotriene treatment for 7 days. In the calcipotriene-treated group, interleukin (IL)-10 levels (pg/microgram of protein) increased by 57% from baseline (0.030 +/- 0.006; mean +/- SEM) to day 3 (0.047 +/- 0.011) (P = 0.05 vs. baseline; n = 10) and remained elevated at day 7 (0.046 +/- 0.012). IL-8 levels (pg/microgram of protein), however, declined by 70% from baseline (0.13 +/- 0.06) to day 3 (0.04 +/- 0.01), and remained low at day 7 (0.03 +/- 0.02) (P < 0.05 vs. baseline; n = 10). Both IL-8 and IL-10 were unaffected by vehicle treatment. Calcipotriene-induced clinical improvement of psoriasis is preceded by an increase in IL-10 and a concomitant decrease in IL-8 levels. The changes in the level of these two cytokines provide further evidence for immunological changes as a significant part of the mechanism of action of calcipotriene in psoriasis.
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PMID:Calcipotriene-induced improvement in psoriasis is associated with reduced interleukin-8 and increased interleukin-10 levels within lesions. 953 26

Dendritic cells (DC) are bone marrow derived cells present in diverse tissues and organs including the skin, mucosae and blood. DC have a capital role in the afferent pathway of the immune response because of its role in up-take, processing and presenting antigens to immune cells. Human DC are usually identified by the expression of surface CD1a and HLA-DR. Despite the significant recent developments for in vitro generation of DC derived from blood by using cytokines like GM-CSF and IL-4, the studies on DC and specially on human Langerhans cells (LC) have been hampered by the laborious isolation procedure and the small yield of cells obtained by the various methods of isolation used so far. Therefore, a priority has been a search for monoclonal dendritic cell-lines with LC characteristics in order to facilitate the research in this area. The present study reports on the generation of two stable, self-replicant, adherent, dendritic, CD1a+, HLA-DR , CD45RO , CD23/FcERII+ cell-lines that up-take and process soluble antigens but also inducing MLR and antigen-dependent T-cell response.
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PMID:Characterisation of two human dendritic cell-lines that express CD1a, take-up, process and present soluble antigens and induce MLR. 956 73

Fluticasone propionate (FP) is a trifluorinated glucocorticoid based on the androstane nucleus. It was selected for development from structure-activity relationships (topical anti-inflammatory, cutaneous vasoconstriction, and hypothalamic-pituitary-adrenal axis suppression) of a series of 17beta-carbothioates. FP is 3-, 300-, and 1000-fold more lipophilic than beclomethasone dipropionate, budesonide, and triamcinolone acetonide, respectively. FP has an absolute affinity (KD) for the glucocorticoid receptor of 0.5 nmol/L and a relative receptor affinity 1.5-fold higher than beclomethasone-17-monopropionate (17-BMP) and mometasone furoate, 3-fold higher than budesonide, and 20-fold higher than flunisolide and triamcinolone acetonide. The rate of association of FP with the receptor is faster and the rate of dissociation slower than other corticosteroids. The resulting half-life of the FP active steroid-receptor complex is >10 hours, compared with approximately 5, 7.5, and 4 hours for budesonide, 17-BMP, and triamcinolone acetonide, respectively. FP has high selectivity for the glucocorticoid receptor, with little or no activity at other steroid receptors. FP is more potent than beclomethasone dipropionate, budesonide, triamcinolone acetonide, and mometasone furoate in inhibiting human T-cell migration and proliferation, inhibiting CD4+ T-cell cytokine and basophil histamine release, attenuating adhesion molecule expression, stimulating inflammatory cell apoptosis, and inducing cellular antiprotease release. In asthma patients, FP decreases the number of CD3+, CD4+, CD8+, and CD25+ T cells, mast cells, and eosinophils in bronchial biopsies, in addition to suppressing CD1a-dendritic and IgE+ cells and HLA-DR. FP, therefore, has a good pharmacologic profile for a topical steroid with increased intrinsic glucocorticoid potency and potent anti-inflammatory activity.
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PMID:Development of fluticasone propionate and comparison with other inhaled corticosteroids. 956 68


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