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

ABSTRACT: 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 i

SUBMITTER: Spurlock CF 

PROVIDER: S-EPMC4506868 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature