Protein tyrosine phosphatase σ regulates autoimmune encephalomyelitis development

Protein tyrosine phosphatases (PTPs) play essential roles in regulating signaling events in multiple cells by tyrosine dephosphorylation. One of them, PTP sigma, appears important in regulating function of plasmacytoid dendritic cells (pDC). Here we report that PTP sigma 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. PTP sigma-/- mice displayed pro inflammatory profiles in the spinal cord and lymphoid organs following MOG peptide immunization. PTP sigma 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, PTP sigma is a key negative regulator in EAE initiation and progression, which acts by regulating functions of DCs, T cells, and other immune cells. PTP sigma may become an important molecular target for treating autoimmune disorders. (C) 2017 Elsevier Inc. All rights reserved.