Protein tyrosine phosphatase ? 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, PTP?, appears important in regulating function of plasmacytoid dendritic cells (pDC). Here we report that PTP? 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?-/- mice displayed pro-inflammatory profiles in the spinal cord and lymphoid organs following MOG peptide immunization. PTP? 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? is a key negative regulator in EAE initiation and progression, which acts by regulating functions of DCs, T cells, and other immune cells. PTP? may become an important molecular target for treating autoimmune disorders.

SUBMITTER: Ohtake Y 

PROVIDER: S-EPMC6275552 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature