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)

It is well established that granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1 and tumour necrosis factor-alpha (TNF-alpha) are involved in Langerhans' cell (LC) development and dendritic cell traffic. However, little is known about the pattern of cytokine receptors on human LC and their modulation during different stages of maturation. The expression of cytokine receptors was studied by flow cytometry on both freshly isolated LC (fLC) and 72-hr cultured LC (cLC). Epidermal cell suspensions enriched in LC were obtained after skin trypsinization and Ficoll-Hypaque gradient. LC were identified by their CD1a positivity. Although the majority of fLC were positive for the alpha chain of GM-CSF receptor (GM-CSFR), the beta chain of GM-CSFR was detected only on 15% of CD1a+ cells. fLC were also positive for IL-1 receptor (IL-1R) type 1, IL-1R type 2, 75,000 molecular weight TNF receptor (TNFR) and interferon-gamma receptor (IFN-gamma R). IL-6R and its transducing signal gp130 were present in a subset of fLC. Granulocyte colony-stimulating factor receptor (G-CSFR), macrophage colony-stimulating factor receptor (M-CSFR), the alpha and beta chain of IL-2R, IL-4R, IL-7R, IL-8R and 55,000 molecular weight TNFR were not detected on fLC. After culture, LC up-regulated the expression of both the alpha and beta chains of GM-CSFR, IL-1R type 2, alpha and beta chains of IL-2R, IL-6R and gp130. In contrast, IL-1R type 1 and 75,000 molecular weight TNFR were down-modulated and the expression of IFN-gamma R was not affected by culture. These results suggest that LC undergo changes in the cytokine receptor repertory during in vitro maturation.
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PMID:Flow cytometric analysis of cytokine receptors on human Langerhans' cells. Changes observed after short-term culture. 869 97

Malignant cells may escape from the immune response in vivo because of a defective differentiation of professional antigen-presenting cells (APCs), i.e., dendritic cells (DCs). We recently reported that tumor cells release interleukin (IL)-6 and macrophage colony stimulating factor (M-CSF), which inhibit the differentiation of CD34+ cells into DCs and promote their commitment toward monocytic lineage with a poor APC function. The results presented here show that both IL-4 and IL-13 reverse the inhibitory effects of renal cell carcinoma conditioned media (RCC CM) or IL-6+M-CSF on the phenotypic and functional differentiation of CD34+ into DCs. IL-4 was found to act through a rapid blockade of the expression of M-CSF and the IL-6 receptor-transducing chain (gp130), along with a decrease of the secondary production of M-CSF, thereby preventing the loss of granulocyte macrophage colony stimulating factor (GM-CSF) receptor alpha chain expression on differentiating CD34+ cells. Consistent with these observations, the differentiation of DCs from monocytes cultured with GM-CSF and IL-4 was also impaired by RCC CM, but the minimal inhibitory concentrations of RCC CM were 10-fold higher than for CD34+ cells. In these conditions, monocytes cultured with GM-CSF and IL-4 also exhibited profound phenotypic changes (CD14+ D32+ CD86+ HLA-DR+ CD115(low) CD23(low) CD1a-) and a poor APC function. These alterations were overcome in a dose-dependent manner by IL-4 (5-500 IU/ml), although not beyond a 40% final concentration of RCC CM. The capacity of RCC CM to block DC differentiation from monocytes strongly correlated with IL-6 and M-CSF concentrations in medium. Taken together, these results demonstrate that IL-4 and IL-13 reverse the inhibitory effect of tumor cells on DC differentiation.
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PMID:IL-4 prevents the blockade of dendritic cell differentiation induced by tumor cells. 1130 93

Interleukin (IL)-6 plays pleiotropic roles in human hematopoiesis and immune responses by acting on not only the IL-6 receptor-alpha subunit (IL-6Ralpha)(+) but also IL-6Ralpha(-) hematopoietic progenitors via soluble IL-6R. The Notch ligand Delta-1 has been identified as an important modulator of the differentiation and proliferation of human hematopoietic progenitors. Here, it was investigated whether these actions of IL-6 are influenced by Delta-1. When CD34(+)CD38(-) hematopoietic progenitors were cultured with stem cell factor, flt3 ligand, thrombopoietin and IL-3, Delta-1, in combination with the IL-6R/IL-6 fusion protein FP6, increased the generation of glycophorin A(+) erythroid cells but counteracted the effects of IL-6 and FP6 on the generation of CD14(+) monocytic and CD15(+) granulocytic cells. Although freshly isolated CD34(+)CD38(-) cells expressed no or only low levels of IL-6Ralpha, its expression was increased in myeloid progenitors after culture but remained negative in erythroid progenitors. It was found that Delta-1 acted in synergy with FP6 to enhance the generation of erythroid cells from the IL-6Ralpha(-) erythroid progenitors. In contrast, Delta-1 antagonized the effects of IL-6 and FP6 on the development of monocytic and granulocytic cells, as well as CD14(-)CD1a(+) dendritic cells, from the IL-6Ralpha(+) myeloid progenitors. These results indicate that Delta-1 interacts differentially with gp130 activation in IL-6Ralpha(-) erythroid and IL-6Ralpha(+) myeloid progenitors. The present data suggest a divergent interaction between Delta-1 and gp130 activation in human hematopoiesis.
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PMID:Notch ligand Delta-1 differentially modulates the effects of gp130 activation on interleukin-6 receptor alpha-positive and -negative human hematopoietic progenitors. 1764 74