| Literature DB >> 34294714 |
Yuzo Koda1,2, Toshiaki Teratani1, Po-Sung Chu1, Yuya Hagihara1, Yohei Mikami1, Yosuke Harada1, Hanako Tsujikawa3, Kentaro Miyamoto1, Takahiro Suzuki1, Nobuhito Taniki1, Tomohisa Sujino1, Michiie Sakamoto3, Takanori Kanai4,5, Nobuhiro Nakamoto6.
Abstract
Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease that can progress to liver fibrosis. Recent clinical advance suggests a reversibility of liver fibrosis, but the cellular and molecular mechanisms underlying NASH resolution remain unclarified. Here, using a murine diet-induced NASH and the subsequent resolution model, we demonstrate direct roles of CD8+ tissue-resident memory CD8+ T (CD8+ Trm) cells in resolving liver fibrosis. Single-cell transcriptome analysis and FACS analysis revealed CD69+CD103-CD8+ Trm cell enrichment in NASH resolution livers. The reduction of liver CD8+ Trm cells, maintained by tissue IL-15, significantly delayed fibrosis resolution, while adoptive transfer of these cells protected mice from fibrosis progression. During resolution, CD8+ Trm cells attracted hepatic stellate cells (HSCs) in a CCR5-dependent manner, and predisposed activated HSCs to FasL-Fas-mediated apoptosis. Histological assessment of patients with NASH revealed CD69+CD8+ Trm abundance in fibrotic areas, further supporting their roles in humans. These results highlight the undefined role of liver CD8+ Trm in fibrosis resolution.Entities:
Mesh：
Substances：
Year: 2021 PMID： 34294714 DOI： 10.1038/s41467-021-24734-0
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919