| Autor: |
Koda, Yuzo, Teratani, Toshiaki, Chu, Po-Sung, Hagihara, Yuya, Mikami, Yohei, Harada, Yosuke, Tsujikawa, Hanako, Miyamoto, Kentaro, Suzuki, Takahiro, Taniki, Nobuhito, Sujino, Tomohisa, Sakamoto, Michiie, Kanai, Takanori, Nakamoto, Nobuhiro |
| Předmět: |
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| Zdroj: |
Nature Communications; 7/22/2021, Vol. 12 Issue 1, p1-15, 15p |
| Abstrakt: |
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. The cellular and molecular mechanisms underlying the resolution of non-alcoholic steatohepatitis remain incompletely understood. Here the authors report a single cell-based analysis that identified CD8 + tissue-resident memory T cells, which contribute to resolution of liver fibrosis potentially via elimination of hepatic stellate cells through Fas-mediated cytotoxicity. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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