Cutting edge: Chronic NF-κB activation in CD4+ T Cells in Rheumatoid Arthritis is Genetically Determined by HLA risk alleles

Charles F. Spurlock, John T. Tossberg, Nancy J. Olsen, Thomas M. Aune

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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-DRB104 genotype, and blocking HLA-DR inhibited NF-κB activity in CD4+ T cells and normalized gene expression, as did pharmacologic inhibition of NFkB. We conclude that interactions between TCR and MHC class II encoded by HLA-DRB104 create a proinflammatory "hum" altering CD4+ T cell phenotype.

Original languageEnglish (US)
Pages (from-to)791-795
Number of pages5
JournalJournal of Immunology
Volume195
Issue number3
DOIs
StatePublished - Aug 1 2015

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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