Protein Tyrosine Phosphatase Inhibition Prevents Experimental Cerebral Malaria by Precluding CXCR3 Expression on T Cells.

ABSTRACT: Cerebral malaria induced by Plasmodium berghei ANKA infection is dependent on the sequestration of cytotoxic T cells within the brain and augmentation of the inflammatory response. Herein, we demonstrate that inhibition of protein tyrosine phosphatase (PTP) activity significantly attenuates T cell sequestration within the brain and prevents the development of neuropathology. Mechanistically, the initial upregulation of CXCR3 on splenic T cells upon T cell receptor stimulation was critically decreased through the reduction of T cell-intrinsic PTP activity. Furthermore, PTP inhibition markedly increased IL-10 production by splenic CD4⁺ T cells by enhancing the frequency of LAG3⁺CD49b⁺ type 1 regulatory cells. Overall, these findings demonstrate that modulatio

SUBMITTER: Van Den Ham KM 

PROVIDER: S-EPMC5511231 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature