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)

Recently, we reported the functional expression of CD86 on cultured human Langerhans cells derived from normal epidermis. In the present study, we investigated the expression and function of co-stimulatory molecules in the pathogenesis of atopic dermatitis. In immunohistochemical analysis, CD80 and/or CD86 were detected on dendritic-shaped cells not only in the epidermis but also in the dermis in the inflammatory lesions of atopic dermatitis (n = 12). CD80 was expressed in only five cases (42%), while CD86 was expressed in all cases (100%). These molecules were not detected in normal control subjects (n = 8). In non-lesional skin of atopic dermatitis (n = 4), CD86 but not CD80 was detected in one case. CD86 was preferentially induced on dendritic-shaped cells in positive patch test sites to Dermatophagoides pteronyssinus or house dust allergen in atopic dermatitis (n = 4). The CD80- or CD86-positive cells were confirmed as Langerhans cells by double immunostaining using anti-CD1a monoclonal antibody. Neither CD86 nor CD80 was detected on keratinocytes. Similar results of the stronger expression of CD86 over that of CD80 were obtained from psoriasis vulgaris (n = 11) and from contact dermatitis (n = 7), although CD86 was expressed only in 57% of the contact dermatitis cases. The percentage of Langerhans cells positive for CD86 was higher than for CD80, i.e. 48% compared with 9%, respectively, in the epidermis of lesional skin of atopic dermatitis (n = 8). The expression rate of these molecules on Langerhans cells increased in the dermis. To investigate the function of co-stimulatory molecules on Langerhans cells in atopic dermatitis, we conducted an inhibition test with antibodies. Anti-CD86 monoclonal antibody almost completely inhibited T-cell proliferation stimulated with crude extract of D. pteronyssinus in the presence of epidermal cells as antigen-presenting cells, whereas anti-CD80 monoclonal antibody produced less of an inhibitory effect. These data indicate that CD86 expressed on Langerhans cells may play an important part in the pathogenesis of atopic dermatitis.
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PMID:Functional CD86 (B7-2/B70) is predominantly expressed on Langerhans cells in atopic dermatitis. 960 93

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

The association between the atopic dermatitis, eczema and T-cell immunodeficiency disorders are well known, thus suggesting that bone marrow T-precursors could use the micro-environment of the skin as an extrathymic site for compensatory ontogenesis. In keeping with this hypothesis, we analyzed the atopic dermatitis skin lymphocytic infiltrate phenotypes to establish their ontogenetic stage of development. Cryostatic sections (4 microns) obtained from acute lesional skin biopsies of six patients with extrinsic atopic dermatitis were processed with indirect immunoperoxidase, using a panel of first-step monoclonal antibodies (mAb) specific to CD104 (integrin beta 4 chain), CD90w (Thy 1 antigen), CD44 (phagocytic glycoprotein-1; Pgp-1), CD1a and the DNA polymerase terminal deoxynucleotidyl transferase (TdT). Within the lymphocytic dermal infiltrate different levels of immunoreactivity were observed with respect to CD104, CD90w and CD1a. A strong, spread staining was also detected for mAb specific to Pgp-1 and TdT. Together, the reported features indicate that the atopic dermatitis skin-homing lymphocytes express immunophenotypes which are distinctive of the early T-ontogeny.
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PMID:Expression of T-lineage early developmental markers by cells establishing atopic dermatitis skin infiltrates. 1002 83

We have recently shown the expression of lymphoid early developmental markers, including CD104, Thy 1, CD1a, Pgp-1 and TdT, by the cells constituting atopic dermatitis skin infiltrates. To further characterize the cellular phenotypes we used an indirect immunoperoxidase assay to analyze sections from two atopic dermatitis lesion skin biopsies using the following as first step monoclonal antibodies (MAB): anti-CD34, CD2, CD5 and CD7. CD34+ mononuclear cells and endothelial cells were identified. A strong immunoreaction was observed for the T-lineage marker CD2 and CD5, but a poor reaction, if any, was seen for the CD7. Since CD34+ marrow and blood cells are currently believed to be the major source of the hemopoietic precursors, our data provide further substantial evidence supporting the hypothesis that the atopic dermatitis skin cell infiltrate represents an ongoing T-lineage in situ differentiation process regulated by the skin epithelial microenvironment. The observed defective expression of the CD7 antigen requires further investigation for its confirmation as a possible constant feature in atopic dermatitis.
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PMID:Hemopoietic progenitor cells in atopic dermatitis skin lesions. 1066 34

Liver-and activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3alpha/CCL20 is a CC chemokine which is constitutively expressed by follicle-associated epithelial cells in the mucosa, and attracts cells expressing CCR6 such as immature dendritic cells and alpha(4)beta(7)(high) intestine-seeking memory T cells. Here, we examine LARC/CCL20 expression in the skin. LARC/CCL20 mRNA and protein were induced in primary human keratinocytes upon stimulation with proinflammatory cytokines such as IL-1alpha and tumor necrosis factor (TNF)-alpha. In mice, intradermal injection of IL-1alpha and TNF-alpha rapidly induced a local accumulation of transcripts for LARC/CCL20 and its receptor CCR6 with a lag of several hours in the latter. In humans, immunostaining of LARC/CCL20 was weak if any in normal skin tissues but strongly augmented in lesional skin tissues with atopic dermatitis. Furthermore, massive infiltration of cells with markers such as CD1a, CD3 or HLA-DR was present in atopic skin lesions. Many infiltrating cells were also found to be CCR6(+) by a newly generated monoclonal anti-CCR6. However, Langerhans cells residing within the epidermis were hardly stained by anti-CCR6 in normal and atopic skin tissues. Furthermore, plasma levels of LARC/CCL20 were found to be elevated in patients with atopic dermatitis. Collectively, our results suggest that epidermal keratinocytes produce LARC/CCL20 upon stimulation with proinflammatory cytokines such as IL-1alpha and TNF-alpha, and attract CCR6-expressing immature dendritic cells and memory/effector T cells into the dermis of inflamed skin such as atopic dermatitis. LARC/CCL20 may not, however, play a major role in homeostatic migration of Langerhans cells into the skin.
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PMID:Inducible expression of a CC chemokine liver- and activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3 alpha/CCL20 by epidermal keratinocytes and its role in atopic dermatitis. 1113 38

Macrophage-derived chemokine (MDC)/CCL22 is a CC chemokine active on dendritic cells (DC), NK cells and Th2 lymphocytes. The present study was aimed at comprehensively investigating MDC production in vitro and in vivo. DC were the most potent producers of MDC among leukocytes tested. Endothelial cells did not produce MDC under a variety of conditions. Signals that induce maturation (lipopolysaccharide, IL-1, TNF, CD40 ligand, recognition of bacteria and yeast) dramatically augmented MDC production, and dexamethasone and vitamin D3 blocked it. Prostaglandin E(2), which blocked the acquisition of IL-12 production and the capacity to promote Th1 generation, did not affect MDC production. Using mass spectrometry-based techniques, DC supernatants were found to contain N-terminally truncated forms of MDC [MDC(3-69), MDC(5-69) and MD(C7-69)] as well as the full-length molecule. In vivo, CD1a(+), CD83(+), MDC(+) DC were found in reactive lymph nodes, and in Langerhans' cell histiocytosis. Skin lesions of atopic dermatitis patients showed that CD1a(+) or CD1b(+) DC, and DC with a CD83(+) phenotype were responsible for MDC production in this Th2-oriented disorder. Thus, DC are the predominant source of MDC in vitro and in vivo under a variety of experimental and clinical conditions. Processing of MDC to MDC(3-69) and shorter forms which do not recognize CCR4 is likely to represent a feedback mechanism of negative regulation.
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PMID:Dendritic cells as a major source of macrophage-derived chemokine/CCL22 in vitro and in vivo. 1124 Dec 86

Epidermal Langerhans cells (LCs) and the high-affinity receptor for IgE (Fc(epsilon)RI) on their surface are considered important in the pathogenesis of atopic dermatitis (AD). We investigated the numbers of epidermal LCs and their Fc(epsilon)RI expression in patients with AD and healthy controls. Biopsy specimens taken from lesional skin from 17 patients with AD, non-lesional skin from five patients with AD and normal skin from five healthy individuals were immunohistochemically stained with a monoclonal antibody against CD1a or with either of two monoclonal antibodies against two different epitopes of Fc(epsilon)RI alpha chain. Many dendritic cells were positively stained with anti-CD1a antibody in the epidermis of each skin sample, and fewer cells were stained with anti-Fc(epsilon)RI antibodies. The numbers of epidermal LCs positive for Fc(epsilon)RI were significantly increased in both lesional and non-lesional skin from AD patients compared with those in normal skin, suggesting important roles of Fc(epsilon)RI+LCs in the pathogenesis of the disease. In contrast, the numbers of total epidermal LCs (CD1a-positive) were decreased in AD lesional skin compared with those in non-lesional skin from AD patients and in normal skin from healthy subjects. Together with our finding that the numbers of epidermal LCs were negatively correlated with the clinical severity of the AD lesions, we concluded that epidermal LCs may decrease in some conditions of AD, probably in lesions with severe inflammation.
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PMID:Enhanced expression of the high-affinity receptor for IgE (Fc(epsilon)RI) associated with decreased numbers of Langerhans cells in the lesional epidermis of atopic dermatitis. 1164 Oct 54

The capability to take up mannosylated protein antigens is important for the biologic function of dendritic cells, as many glycoproteins derived from bacteria and fungi, e.g., Malassezia furfur, are mannosylated. The expression of the mannose receptor CD206 has been regarded a differentiation hallmark of immature dendritic cells, whereas monocytes and mature dendritic cells as well as epidermal Langerhans cells do not express CD206. This study describes some epidermal dendritic cells that may express CD206 under inflammatory skin conditions: Immunohistochemical and flow cytometric analysis with the CD206-specific D547 antibody confirmed that Langerhans cells from normal human skin do not express CD206. Epidermal cell suspensions from atopic dermatitis and psoriasis revealed two distinct subsets of epidermal dendritic cells: a CD1a(+++)/CD206(-) cell population (i.e., Langerhans cells) and a CD1a(+)/CD206(++) cell population, corresponding to the previously described inflammatory dendritic epidermal cells. CD206-mediated endocytosis, assessed by dextran-fluorescein isothiocyanate uptake, was demonstrated in inflammatory dendritic epidermal cells but not in Langerhans cells. CD206-independent uptake of the fluorescent dye Lucifer yellow, a pinocytosis marker, was demonstrated in both Langerhans cells and inflammatory dendritic epidermal cells. Electron microscopic examination, known to distinguish Langerhans cells from inflammatory dendritic epidermal cells by their Birbeck granules, revealed Langerhans cells with Birbeck granules and inflammatory dendritic epidermal cells without Birbeck granules. Inflammatory dendritic epidermal cells exhibited numerous coated pits and vesicles, the latter fusing with large endosome-like structures, thus suggesting a high endocytotic activity. Immunogold staining with D547 monoclonal antibody confirmed that inflammatory dendritic epidermal cells were positive for CD206. In conclusion, inflammatory dendritic epidermal cells but not Langerhans cells are expressing CD206 in situ and use it for receptor-mediated endocytosis.
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PMID:Expression and function of the mannose receptor CD206 on epidermal dendritic cells in inflammatory skin diseases. 1184 52

During pregnancy, maternal cells may enter the fetal circulation and persist until adulthood. The fate of these cells remains unknown. As unexplained T-cell-mediated conditions such as pityriasis lichenoides (PL) may occur in children, we aimed at identifying maternal cells in lesional skin of PL and controls. Archived skin biopsy specimens from young males with PL, atopic dermatitis, or normal skin were scanned for the presence of female (presumably maternal) cells using fluorescence in situ hybridization (FISH) with X and Y chromosome-specific probes. Phenotyping of maternal cells relied on FISH combined with anti-CD45, anti-CD1a, or anti-cytokeratin labelling, identifying leukocytes, Langerhans cells, and keratinocytes, respectively. Maternal cells were found in PL (11/12) and controls (4/7), but their average frequency was higher in PL: 99 per million cells as compared to 5 per million cells in controls (P = 0.005). In the epidermis, the maternal microchimeric cells were labelled by anti-cytokeratin in all cases. We identified maternally derived keratinocytes in the skin of male children with inflammatory skin disorders. These cells may either help repair the damaged skin or home initially in the skin and trigger a host (child) versus graft (mother) disease.
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PMID:Presence of chimeric maternally derived keratinocytes in cutaneous inflammatory diseases of children: the example of pityriasis lichenoides. 1641 31

Staphylococcus aureus may perform an crucial function in atopic dermatitis (AD), via the secretion of superantigens, including staphylococcal enterotoxins (SE) A or B, and toxic shock syndrome toxin-1 (TSST-1). Dysregulated cytokine production by keratinocytes (KCs) upon exposure to staphylococcal superantigens (SsAgs) may be principally involved in the pathophysiology of AD. We hypothesized that lesional KCs from AD may react differently to SsAgs compared to nonlesional skin or normal skin from nonatopics. We conducted a comparison of HLA-DR or CD1a expression in lesional skin as opposed to that in nonlesional or normal skin by immunohistochemistry (IHC). We also compared, using ELISA, the levels of IL-1alpha, IL-1beta, and TNF-alpha secreted by cultured KCs from lesional, nonlesional, and normal skin, after the addition of SEA, SEB and TSST-1. IHC revealed that both HLA-DR and CD1a expression increased significantly in the epidermis of lesional skin versus nonlesional or normal skin in quite a similar manner. IL-1alpha, IL-1beta, and TNF-alpha secretion was also significantly elevated in the cultured KCs from lesional skin after the addition of SsAgs. Our results indicated that KCs from lesional skin appear to react differently to SsAgs and increased proinflammatory cytokine production in response to SsAgs may contribute to the pathogenesis of AD.
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PMID:Role of staphylococcal superantigen in atopic dermatitis: influence on keratinocytes. 1661 21


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