Cutting Edge: Chronic NF-κB Activation in CD4+ T Cells in Rheumatoid Arthritis Is Genetically Determined by HLA Risk Alleles

Autor:	Nancy J. Olsen, John T. Tossberg, Charles F. Spurlock, Thomas M. Aune
Rok vydání:	2015
Předmět:	musculoskeletal diseases MHC class II biology Lymphocyte T cell Immunology T-cell receptor Human leukocyte antigen TCIRG1 Interleukin 21 medicine.anatomical_structure medicine biology.protein Immunology and Allergy Cytotoxic T cell skin and connective tissue diseases
Zdroj:	The Journal of Immunology. 195:791-795
ISSN:	1550-6606 0022-1767
DOI:	10.4049/jimmunol.1500267
Popis:	Of identified genetic variants, HLA polymorphisms confer the greatest risk for developing autoimmune diseases, including rheumatoid arthritis (HLA-DRB1*04). There are strong influences of HLA polymorphisms on cell type–specific gene expression in B cells and monocytes. Their influence on gene expression in CD4+ T cells is not known. We determined transcript and proteins levels of target genes in lymphocyte/monocyte subsets in healthy controls and rheumatoid arthritis subjects as a function of HLA-DRB1*04 haplotype. We identified gene expression dependent on HLA-DRB1*04 genotype in CD4+ T cells. NF-κB activity in CD4+ T cells was also dependent on HLA-DRB1*04 genotype, and blocking HLA-DR inhibited NF-κB activity in CD4+ T cells and normalized gene expression, as did pharmacologic inhibition of NF-κB. We conclude that interactions between TCR and MHC class II encoded by HLA-DRB1*04 create a proinflammatory “hum” altering CD4+ T cell phenotype.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::4b937764110273301d33a5abf92d2620 https://doi.org/10.4049/jimmunol.1500267 Zobrazit plný text záznamu