| First Author | Xu J | Year | 2019 |
| Journal | Front Immunol | Volume | 10 |
| Pages | 1980 | PubMed ID | 31481966 |
| Mgi Jnum | J:288022 | Mgi Id | MGI:6415887 |
| Doi | 10.3389/fimmu.2019.01980 | Citation | Xu J, et al. (2019) Tpl2 Protects Against Fulminant Hepatitis Through Mobilization of Myeloid-Derived Suppressor Cells. Front Immunol 10:1980 |
| abstractText | 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 hepatocytes to mediate the induction of MDSC-attracting chemokine CXCL1 and CXCL2 through modulating IL-25 (also known as IL-17E) signaling. As a consequence, increased MDSC in the inflamed liver specifically restrained the local proliferation of infiltrated pathogenic CD4(+) T cells, and thus protected against the inflammation-induced acute liver failure. Together, our findings established Tpl2 as a critical mediator of MDSC recruitment and highlighted the therapeutic potential of Tpl2 for the treatment of FH. |
