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Protein tyrosine phosphatase σ regulates autoimmune encephalomyelitis development.

Abstract
Protein tyrosine phosphatases (PTPs) play essential roles in regulating signaling events in multiple cells by tyrosine dephosphorylation. One of them, PTPσ, appears important in regulating function of plasmacytoid dendritic cells (pDC). Here we report that PTPσ deletion in knockout mice and inhibition with a selective antagonist peptide exacerbated symptoms of experimental autoimmune encephalomyelitis (EAE) by enhancing axon and myelin damage in the spinal cord. PTPσ-/- mice displayed pro-inflammatory profiles in the spinal cord and lymphoid organs following MOG peptide immunization. PTPσ deletion promoted a pro-inflammatory phenotype in conventional DCs and directly regulated differentiation of CD4+ T cells. It also facilitated infiltration of T lymphocytes, activation of macrophages in the CNS and development of EAE. Therefore, PTPσ is a key negative regulator in EAE initiation and progression, which acts by regulating functions of DCs, T cells, and other immune cells. PTPσ may become an important molecular target for treating autoimmune disorders.
AuthorsYosuke Ohtake, Weimin Kong, Rashad Hussain, Makoto Horiuchi, Michel L Tremblay, Doina Ganea, Shuxin Li
JournalBrain, behavior, and immunity (Brain Behav Immun) Vol. 65 Pg. 111-124 (Oct 2017) ISSN: 1090-2139 [Electronic] Netherlands
PMID28559011 (Publication Type: Journal Article)
CopyrightCopyright © 2017 Elsevier Inc. All rights reserved.
Chemical References
  • Cytokines
  • Myelin-Oligodendrocyte Glycoprotein
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
Topics
  • Animals
  • Cell Differentiation
  • Cytokines (metabolism)
  • Dendritic Cells (metabolism)
  • Encephalomyelitis, Autoimmune, Experimental (immunology, metabolism, physiopathology)
  • Lymphocyte Activation
  • Macrophages (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Myelin Sheath (metabolism)
  • Myelin-Oligodendrocyte Glycoprotein (immunology)
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 (metabolism, physiology)
  • Spinal Cord (metabolism)
  • T-Lymphocytes (immunology)

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