Tpl2 Protects Against Fulminant Hepatitis Through Mobilization of Myeloid-Derived Suppressor Cells.

ABSTRACT: Myeloid derived suppressor cells (MDSC) in the liver microenvironment protects against the inflammation-induced liver injury in fulminant hepatitis (FH). However, the molecular mechanism through which MDSC is recruited into the inflamed liver remain elusive. Here we identified a protein kinase Tpl2 as a critical mediator of MDSC recruitment into liver during the pathogenesis of Propionibacterium acnes/LPS-induced FH. Loss of Tpl2 dramatically suppressed MDSC mobilization into liver, leading to exaggerated local inflammation and increased FH-induced mortality. Mechanistically, although the protective effect of Tpl2 for FH-induced mortality was dependent on the presence of MDSC, Tpl2 neither directly targeted myeloid cells nor T cells to regulate FH pathogenesis, but functioned in hep

SUBMITTER: Xu J 

PROVIDER: S-EPMC6710335 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature