Loss of β-arrestin 2 exacerbates experimental autoimmune encephalomyelitis with reduced number of Foxp3+ CD4+ regulatory T cells

Immunology. 2013 Dec;140(4):430-40. doi: 10.1111/imm.12152.

Abstract

β-Arrestins are well-known regulators and mediators of G protein-coupled receptor signalling, and accumulating evidence reveals that they are functionally involved in inflammation and autoimmune diseases. Of the two β-arrestins, β-arrestin 1 is documented to play regulatory roles in an animal model of multiple sclerosis (MS), whereas the role of β-arrestin 2 is less clear. Here, we show that β-arrestin 2-deficient mice displayed the exacerbated and sustained symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. At the cellular level, deficiency of β-arrestin 2 led to a decreased number of Foxp3(+) CD4(+) regulatory T (Treg) cells in peripheral lymphoid organs of EAE mice. Consistently, our in vitro observations also revealed that loss of β-arrestin 2 impaired the conversion of Foxp3(-) CD4(+) T cells into Foxp3(+) CD4(+) inducible Treg cells. Taken together, our data suggest that β-arrestin 2 plays a regulatory role in MS, that is opposite to that of β-arrestin 1, in autoimmune diseases such as MS, which is at least partially through regulation of iTreg cell differentiation.

Keywords: experimental autoimmune encephalomyelitis; regulatory T cells; β-arrestin 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrestins / deficiency*
  • Arrestins / genetics
  • CD4 Lymphocyte Count
  • Cell Differentiation
  • Central Nervous System / immunology
  • Central Nervous System / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Time Factors
  • beta-Arrestin 1
  • beta-Arrestin 2
  • beta-Arrestins

Substances

  • Arrb1 protein, mouse
  • Arrb2 protein, mouse
  • Arrestins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • beta-Arrestin 1
  • beta-Arrestin 2
  • beta-Arrestins
  • Green Fluorescent Proteins