UNIPROT:P06126 - FACTA Search

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)

Human monocytes cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-13 for 7 days differentiate into cells with the morphology and function of dendritic cells (DC). We have investigated the effect of IL-10 on this differentiation pathway. In the presence of IL-10 cells did not develop DC morphology, did not express CD1a and had lower levels of MHC class II. IL-10 promoted the differentiation of large cells with the morphology, cytochemistry and membrane phenotype of macrophages, including staining for nonspecific esterase and high levels of CD14, CD16 and CD68. The effect of IL-10 was dose dependent and was best appreciated when the cytokine was added at the initiation of the culture, as addition on day 3 was less inhibitory. When added to already differentiated DC on day 6, IL-10 caused only a modest reduction of MHC class II and CD1a expression, and no acquisition of the macrophage markers CD14, CD16 and CD68. Prolonged incubation up to 5 days with IL-10 did not induce a shift of differentiated DC to macrophages. On the other hand, the macrophages obtained by culturing for 7 days with GM-CSF+IL-13+IL-10 did not shift to DC upon removal of IL-10 for up to 3 days. Thus, the effect of IL-10 on monocyte differentiation, occurs only at the precursor level and confers an irreversible phenotype. From a functional point of view, cells cultured in the presence of IL-10 were poor stimulators of allogeneic cord blood T cells in mixed lymphocyte reaction (MLR) and presented tetanus toxin (TT) to specific T cell lines with much less efficiency than control DC. In contrast, IL-10-cultured DC showed 7 times greater endocytosis of FITC-dextran. This increased endocytosis was mostly mediated via the mannose receptor, as demonstrated by blocking with unlabeled mannose. In conclusion, IL-10 inhibits DC differentiation from monocytes and, in a substantial proportion of the cells, promotes the differentiation to mature macrophages. Intriguingly, IL-10 inhibits antigen presentation while it stimulates endocytic activity.
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PMID:IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages. 948 15

The CD1 molecules have been shown to present non-protein antigens, such as complex lipids to Mycobacteria, and may be important in presenting glycolipids which are involved in inflammatory neuropathies. To study the expression of CD1 molecules in peripheral nerve, we examined nerve biopsies from two patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), five with acute axonal neuropathy, six with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), nine with chronic axonal neuropathy, six with vasculitic neuropathy and three with no histological abnormality. Immunocytochemical studies showed strong labelling of CD1b on endoneurial macrophages (CD68+) and on myelinated nerve fibres in both AIDP patients, but it was rarely observed in the other patients. Weaker staining was seen on endoneurial macrophages and/or other endoneurial cells in some of the patients with other peripheral neuropathies, but none of the control nerves. CD1a had a weaker, but similar pattern. There was endoneurial infiltration of CD4+ and CD8+ T cells in the AIDP and CIDP nerves and sometimes in the other peripheral neuropathy nerves, but not in the normal nerves. Most T cells had alpha beta+ T cell receptors (TCR), but gamma delta+ TCR T cells were found in the nerves of both AIDP patients and sometimes in the nerves of other patients with peripheral neuropathy. Staining for mannose receptor was almost universal, being more intense in AIDP, chronic axonal neuropathy and vasculitis patients. We conclude that CD1 molecule expression is upregulated in peripheral neuropathy, especially in association with inflammation.
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PMID:The distribution of CD1 molecules in inflammatory neuropathy. 970 86

Human monocyte-derived dendritic cells were differentiated in vitro for 7 days with granulocyte macrophage-colony stimulating factor and interleukin-13. These cultured dendritic cells are at an immature stage of differentiation and exhert high endocytic activity via surface mannose receptor and via fluid-phase macropinocytosis. We have investigated the modulation of endocytosis by interleukin-10 in these cells. When added during the last 24 h of the 7-day culture, interleukin-10 significantly stimulated the uptake of fluorescein-labelled dextran (39 +/- 16% increase, mean +/- SD of 6 experiments), a sugar binding to the mannose receptor. This effect was dose dependent and correlated with the length of exposure to interleukin-10, with a maximal effect (more than seven-fold increase) when the cytokine was added at the beginning of the culture (day 0). The interleukin-10-increased fluorescein-labelled-dextran endocytosis was mostly mediated via the mannose receptor, as unlabelled mannose and specific antimannose receptor monoclonal antibody inhibited most of the uptake. Moreover, interleukin-10-treated cells expressed increased levels (up to four-fold) of mannose receptor. Interleukin-10 also increased, although to a lesser extent, the fluid-phase endocytosis (macropinocytosis) of fluorescein-labelled albumin. Interleukin-10 had the opposite effect on the differentiation and functional activity of monocyte-derived dendritic cells; cells having a very low stimulatory capacity and reduced expression of MHC class II and CD1a after a 7-day exposure. Thus interleukin-10 had a strong immunosuppressive effect on the differentiation and functional activity of monocyte-derived dendritic cells and yet strongly stimulated endocytosis in these cells. We speculate that an increased endocytic activity would eventually result in a decreased availability of antigens in the external milieu, thus contributing to the immunosuppressive and tolerogenic activity of interleukin-10.
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PMID:Interleukin-10 increases mannose receptor expression and endocytic activity in monocyte-derived dendritic cells. 980 26

Sugar receptors are being increasingly implicated in host-pathogen interactions because of their specific recognition of carbohydrates of microorganisms. The aim of this study was to identify sugar receptors expressed on the surface of human epidermal Langerhans cells (LC). To this end, binding of a panel of fluorescent neoglycoproteins to human epidermal LC was analyzed by quantitative flow cytofluorometry after standardization with calibrated beads. We demonstrate that fresh human LC are the only cells isolated from healthy epidermis which express a membrane receptor specific for fucose-bovine serum albumin (BSA) and mannose-BSA. Quantitative analysis of mannose-BSA or fucose-BSA binding showed non-linear Scatchard plots, denoting the presence of high and moderate affinity binding on the LC surface. The binding parameters of these two ligands were not significantly different. Mannan, the yeast mannose-rich polysaccharide, fucose-BSA, mannose-BSA and free fucose are strong competitors of the three known ligands of the mannose receptor, i.e. fucose-BSA, mannose-BSA and fluorescein isothiocyanate dextran. The amount of mannose-BSA and fucose-BSA bound to LC was 1.5-fold higher at 37 degrees C than at 4 degrees C, suggesting an internalization process. Antibodies raised against the human macrophage mannose receptor strongly stained CD1a-positive LC but not CD1a-negative population. Taken together, our data demonstrate that fresh human LC are the only cells in the epidermis to express a fucose-mannose receptor on their surface.
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PMID:Human epidermal Langerhans cells express the mannose-fucose binding receptor. 984 97

Because dendritic cells (DC) play a major role in the initiation of T cell-mediated immunity, we studied the effects of glucocorticoids, well-known inhibitors of the immune and inflammatory response, on the differentiation and maturation of human DC. DC were differentiated from human monocytes by culture with GM-CSF and IL-4 for 7 days with and without dexamethasone (Dex). Cells treated with Dex (10-8 M) (Dex-DC) developed a characteristic dendritic morphology; however, membrane phenotype analysis demonstrated that they were not fully differentiated. Dex-DC expressed low levels of CD1a and, unlike untreated cells, high levels of CD14 and CD16. Molecules involved in Ag presentation (CD40, CD86, CD54) were also impaired. In contrast, molecules involved in Ag uptake (mannose receptor, CD32) and cell adhesion (CD11/CD18, CD54) were up-regulated. After exposure to TNF-alpha or CD40 ligand, Dex-DC expressed lower levels of CD83 and CD86 than untreated cells. Dex-DC showed a higher endocytic activity, a lower APC function, and a lower capacity to secrete cytokines than untreated cells. Overall, these results indicate that DC differentiated in the presence of Dex are at a more immature stage. Moreover, Dex also partially blocked terminal maturation of already differentiated DC. In conclusion, our data suggest that glucocorticoids may act at the very first step of the immune response by modulating DC differentiation, maturation, and function.
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PMID:Glucocorticoids affect human dendritic cell differentiation and maturation. 1035 62

Dendritic cells are critical for the induction of both primary immune responses and immunological tolerance, as well as for the regulation of T-helper 1 (Th1) and 2 (Th2) immune responses. As neonates are notably deficient in Th1 response and cord blood transplantation is noted to result in less graft-versus-host disease (GvHD), we compared the phenotypic and functional characteristics of monocyte-derived dendritic cells (DCs) that favour Th1 development from cord blood and adult peripheral blood to understand the underlying mechanisms of these observations. Our results showed that: (1) after culture for 7 d with interleukin (IL)-4 and granulocyte--macrophage colony-stimulating factor (GM-CSF), cord blood monocytes generated less CD1a(+) cells than adult peripheral blood monocytes, and the CD1a+ cell percentage decreased thereafter; (2) compared with adult blood DCs, cord blood DCs had reduced intensity of expression of CD1a and MHC class II molecules, but the expression levels of CD11c and CD86 were similar; (3) the endocytotic ability of cord blood DCs was reduced compared with adult blood DCs, and this function was related to reduced mannose receptor (MR)-positive cells; (4) furthermore, the ability of cord blood DCs to stimulate CD3(+) T cells in an allogeneic mixed lymphocyte reaction was significantly lower than that of adult blood DCs. These results suggested that the dysfunction of cord blood monocytes in differentiating into professional DCs will affect the activation of naive T cells, especially Th1 development, and may be related to the susceptibility to different infections in the neonates, as well as the lower incidence of GvHD in cord blood transplantation.
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PMID:Decreased yield, phenotypic expression and function of immature monocyte-derived dendritic cells in cord blood. 1132 7

The local cytokine environment and the presence of stimulatory signals determine whether circulating monocytes will finally acquire characteristics of dendritic cells (DCs) or macrophages. Because FcepsilonRI expressed on professional APCs, e.g., monocytes and DCs, has been suggested to play a key role in the pathophysiology of atopic diseases, we evaluated the effect of receptor ligation on the generation of monocyte-derived DCs (MoDCs). Aggregation of FcepsilonRI at the initiation of the IL-4-GM-CSF-driven differentiation resulted in the emergence of macrophage-like cells with a strong expression of the mannose receptor and a low level of CD1a and the DC-specific markers CD83 and the actin-bundling protein (p55). These cells sustained the ability to take up FITC-labeled Escherichia coli by phagocytosis and were significantly less efficient in stimulating purified allogeneic T cells. In addition, receptor ligation of FcepsilonRI at the beginning of the culture prevented the generation of MoDCs, mainly due to a dramatic increase in the IL-10 production. These results suggest that FcepsilonRI aggregation prevents the generation of CD1a(+) MoDCs and imply a novel pivotal function of this receptor in modulating the differentiation of monocytes.
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PMID:Engagement of Fc epsilon RI on human monocytes induces the production of IL-10 and prevents their differentiation in dendritic cells. 1144 Oct 85

Dendritic cells (DC) with potentially important clinical applications have been generated from human peripheral blood monocytes and CD34(+) cells in the presence of recombinant cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-4 (IL-4) and GM-CSF + tumor necrosis factor-alpha (TNF-alpha), respectively. Many of the studies generating DC have included fetal calf serum, which is not desirable due to the risk of immune reactions and infectious disease transmission. Additionally, low DC yields have been reported using serum-free media. In this study, we investigate supplementing serum-free media with autologous serum and plasma for DC generation from monocytes and CD34(+) cells. Our results show that functional DC can be reproducibly obtained in the presence of autologous serum using monocytes and CD34(+) cells as the starting populations. However, with the addition of autologous serum, a differential effect is observed in the phenotypic characterization of these culture-derived DC. Monocytes cultured for 7 days in X-VIVO 15 serum-free media in the presence of GM-CSF + IL-4 showed down-regulation of CD14 with increased expression of HLA-DR, mannose receptor, CD80, and CD86, along with highly up-regulated CD1a(+) expression. The addition of autologous serum to serum-free media in monocyte cultures resulted in a dose-dependent decrease in the CD1a(+) expression generating a distinct subset of CD1a(+/-) cells expressing HLA-DR, mannose receptor, CD80, and CD86. Upon stimulation with CD40L cells, both monocyte-derived DC subsets CD1a(+/-) and CD1a(++) were capable of maturation measured by CD83 and CD86 up-regulation. Data suggest the differences in the monocyte-derived DC in serum-free (CD1a(++)) or autologous serum (CD1a(+/-)) supplemented cultures is of a qualitative nature, rather than quantitative. CD1a(+) and CD14(+) cells expressing HLA-DR, mannose receptor, CD80, and CD86 were generated in 7 days from CD34(+) cells in serum-free media. A quantitative effect was obtained when cultures were supplemented with autologous serum, resulting in a significant enhancement of CD34-derived DC generated. These results demonstrate generation of DC from two different starting populations using serum-free media that can be enhanced with the addition of autologous serum. Interestingly, a differential effect was observed in the phenotypic characterization of these culture-derived DC.
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PMID:Differential effects of autologous serum on CD34(+) or monocyte-derived dendritic cells. 1152 39

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

Human immunodeficiency virus (HIV)-1 Nef protein is an essential modulator of AIDS pathogenesis and we have previously demonstrated that rNef enters uninfected human monocytes and induces T cells bystander activation, up-regulating IL-15 production. Since dendritic cells (DCs) play a central role in HIV-1 primary infection we investigated whether rNef affects DCs phenotypic and functional maturation in order to define its role in the immunopathogenesis of AIDS. We found that rNef up-regulates the expression on immature DCs of surface molecules known to be critical for their APC function. These molecules include CD1a, HLA-DR, CD40, CD83, CXCR4, and to a lower extent CD80 and CD86. On the other hand, rNef down-regulates surface expression of HLA-ABC and mannose receptor. The functional consequence of rNef treatment of immature DCs is a decrease in their endocytic and phagocytic activities and an increase in cytokine (IL-1beta, IL-12, IL-15, TNF-alpha) and chemokine (MIP-1alpha, MIP-1beta, IL-8) production as well as in their stimulatory capacity. These results indicate that rNef induces a coordinate series of phenotypic and functional changes promoting DC differentiation and making them more competent APCs. Indeed, Nef induces CD4(+) T cell bystander activation by a novel mechanism involving DCs, thus promoting virus dissemination.
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PMID:HIV-1 Nef induces dendritic cell differentiation: a possible mechanism of uninfected CD4(+) T cell activation. 1196 93

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