| Literature DB >> 33510172 |
Guangyong Sun1,2,3,4,5, Xinyan Zhao6, Mingyang Li2,3,4,5, Chunpan Zhang2,3,4,5, Hua Jin2,3,4,5, Changying Li2,3,4,5, Liwei Liu6, Yaning Wang2,3,4,5, Wen Shi2,3,4,5, Dan Tian2,3,4,5, Hufeng Xu2,3,4,5, Yue Tian2,3,4,5, Yongle Wu7, Kai Liu2,3,4,5, Zhongtao Zhang8,9,10, Dong Zhang11,12,13,14,15,16.
Abstract
Hepatic inflammation is the driving force for the development and progression of NASH. Treatment targeting inflammation is believed to be beneficial. In this study, adoptive transfer of CD4+ T cells converted double negative T cells (cDNT) protects mice from diet-induced liver fat accumulation, lobular inflammation and focal necrosis. cDNT selectively suppress liver-infiltrating Th17 cells and proinflammatory M1 macrophages. IL-10 secreted by M2 macrophages decreases the survival and function of cDNT to protect M2 macrophages from cDNT-mediated lysis. NKG2A, a cell inhibitory molecule, contributes to IL-10 induced apoptosis and dampened suppressive function of cDNT. In conclusion, ex vivo-generated cDNT exert potent protection in diet induced obesity, type 2 diabetes and NASH. The improvement of outcome is due to the inhibition on liver inflammatory cells. This study supports the concept and the feasibility of potentially utilizing this autologous immune cell-based therapy for the treatment of NASH.Entities:
Year: 2021 PMID： 33510172 PMCID： PMC7844244 DOI： 10.1038/s41467-021-20941-x
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919