Integrin alpha L controls the homing of regulatory T cells during CNS autoimmunity in the absence of integrin alpha 4

Sci Rep. 2015 Jan 16;5:7834. doi: 10.1038/srep07834.

Abstract

Experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), results from an autoimmune attack of the central nervous system (CNS) by effector T helper (Th) 1 and Th17 cells. Regulatory T cells (Treg) can control effector T cells and limit the progression of CNS autoimmunity. Integrin alpha 4 (Itga4) is critical for the entry of Th1 but not Th17 cells into the CNS during EAE. Whether Itga4 controls the homing of Tregs in the CNS and whether Tregs can limit Th17-mediated EAE has, however, not been addressed. Through selective elimination of Itga4 in Foxp3-expressing cells, we show here that Tregs can suppress Th17-mediated EAE and enter into the CNS independently of Itga4. Furthermore, similarly to Th17 cells and in contrast to Th1 cells, Tregs depend on LFA-1 for their entry into the CNS in the absence of Itga4. Therefore, these data suggest that the efficacy of Itga4 neutralization on MS progression may be associated with the prevention of Th1 cells and the maintenance of Tregs migration into the CNS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity*
  • CD11a Antigen / genetics
  • CD11a Antigen / metabolism*
  • Cell Differentiation
  • Central Nervous System / immunology
  • Central Nervous System / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Forkhead Transcription Factors / metabolism
  • Integrin alpha4 / genetics
  • Integrin alpha4 / metabolism*
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • CD11a Antigen
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Lymphocyte Function-Associated Antigen-1
  • Integrin alpha4