Critical regulation of CD4+ T cell survival and autoimmunity by beta-arrestin 1

Nat Immunol. 2007 Aug;8(8):817-24. doi: 10.1038/ni1489. Epub 2007 Jul 8.

Abstract

CD4+ T cells are important in adaptive immunity, but their dysregulation can cause autoimmunity. Here we demonstrate that the multifunctional adaptor protein beta-arrestin 1 positively regulated naive and activated CD4+ T cell survival. We found enhanced expression of the proto-oncogene Bcl2 through beta-arrestin 1-dependent regulation of acetylation of histone H4 at the Bcl2 promoter. Mice deficient in the gene encoding beta-arrestin 1 (Arrb1) were much more resistant to experimental autoimmune encephalomyelitis, whereas overexpression of Arrb1 increased susceptibility to this disease. CD4+ T cells from patients with multiple sclerosis had much higher Arrb1 expression, and 'knockdown' of Arrb1 by RNA-mediated interference in those cells increased apoptosis induced by cytokine withdrawal. Our data demonstrate that beta-arrestin 1 is critical for CD4+ T cell survival and is a factor in susceptibility to autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Arrestins / immunology
  • Arrestins / metabolism*
  • Autoimmunity*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Survival / immunology
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Epigenesis, Genetic
  • Flow Cytometry
  • Humans
  • Immunoblotting
  • Mice
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • beta-Arrestin 1
  • beta-Arrestins

Substances

  • ARRB1 protein, human
  • Arrb1 protein, mouse
  • Arrestins
  • Proto-Oncogene Proteins c-bcl-2
  • beta-Arrestin 1
  • beta-Arrestins