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• W1970319659 abstract "Major histocompatibility complex (MHC) class II deficiency is an inherited autosomal recessive combined immunodeficiency, characterized by a lack of constitutive expression of the human leukocyte antigen (HLA) class II genes. The patients investigated in this study are histoidentical twin brothers with a new phenotype in MHC class II deficiency. Examination of HLA-D locus genes in their fractionated peripheral mononuclear cells (MNCs) revealed an unusual and uncoordinated mRNA pattern. Here we analyzed the distribution of pro- and anti-inflammatory cytokines expressed in these patients' adherent and nonadherent MNCs. We show that gene expression of IL-1α, IL-1β, IL-6, granulocyte–colony-stimulating factor, and IL-10 was induced in both cell fractions, whereas increased mRNA levels of interferon-γ and the inducible nitric oxide synthase were exclusively detected in the patients' nonadherent MNCs. As IL-10 is known to be able to downregulate transcription of MHC class II and expression of IL-10 in the patients' MNCs was increased, we investigated the regulatory function of this cytokine. Interestingly, inhibition of IL-10 protein synthesis with IL-10-specific antisense oligonucleotide DNA (IL-10-AS-ODN) induced HLA-D locus genes in these MHC class II-deficient patients. Exposure of the nonadherent cell fraction to IL-10-AS-ODN resulted in a profound induction of a previously absent DRβ1and DPα gene expression. HLA-DQβ mRNA levels, however, were increased in both the adherent and the nonadherent MNC population. Albeit expression of HLA-D locus genes was inducible via inhibition of IL-10 translation, surface expression of HLA class II antigens on the patients' MNCs was essentially negative. The data presented support the concept of a coordinated network of pro- and anti-inflammatory cytokine regulation and this network obviously has a significant role in the cell-type-specific regulation of MHC class II expression." @default.
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• W1970319659 date "1997-09-01" @default.
• W1970319659 modified "2023-09-23" @default.
• W1970319659 title "Inhibition of IL-10 Protein Synthesis Induces Major Histocompatibility Complex Class II Gene Expression in Class II-Deficient Patients" @default.
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• W1970319659 doi "https://doi.org/10.1006/cimm.1997.1170" @default.
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