CD8+ tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells
Yuzo Koda,Yuzo Koda,Toshiaki Teratani,Po Sung Chu,Yuya Hagihara,Yohei Mikami,Yosuke Harada,Hanako Tsujikawa,Kentaro Miyamoto,Takahiro Suzuki,Nobuhito Taniki,Tomohisa Sujino,Michiie Sakamoto,Takanori Kanai,Takanori Kanai,Nobuhiro Nakamoto +15 more
Reads0
Chats0
TLDR
In this article, using a murine diet-induced NASH and the subsequent resolution model, the authors demonstrate direct roles of CD8+ tissue-resident memory CD8+, T (CD8+ Trm) cells in resolving liver fibrosis.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.read more
Citations
More filters
Journal ArticleDOI
Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease - novel insights into cellular communication circuits.
Moritz Peiseler,Robert F. Schwabe,Jochen Hampe,Paul Kubes,Mathias F. Heikenwälder,Frank Tacke +5 more
TL;DR: In this article , the authors highlight the recent discoveries related to inflammation in NAFLD, discuss the role of immune cell subsets during the different stages of the disease and integrate the multiple systems driving inflammation.
Journal ArticleDOI
Blocking PD-L1–PD-1 improves senescence surveillance and ageing phenotypes
Teh Wei Wang,Yoshikazu Johmura,Narumi Suzuki,Satotaka Omori,Toshiro Migita,Ken Yamaguchi,Seira Hatakeyama,Satoshi Yamazaki,Eigo Shimizu,Seiya Imoto,Yoichi Furukawa,Akihiko Yoshimura,Makoto Nakanishi +12 more
Journal ArticleDOI
Emerging Roles of T Cells in the Pathogenesis of Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma.
TL;DR: In this article, the authors summarized the current knowledge regarding the T cell-mediated mechanisms of inflammation in NASH and discussed the potential therapeutic strategies targeting T-cell-mediated responses for the treatment of NASH.
Journal ArticleDOI
T cells: Friends and foes in NASH pathogenesis and hepatocarcinogenesis
TL;DR: This article will review the specific functions of several T‐cell populations involved in NAFLD andNAFLD‐driven HCC, and illustrate the cellular crosstalk with other immune cells, regulatory networks or stimulatory effects of these interactions, and role of the metabolic microenvironment in influencing immune cell functionality.
Journal ArticleDOI
Liver Fibrosis and MAFLD: From Molecular Aspects to Novel Pharmacological Strategies.
Weiyi Qu,Tengfei Ma,Jingjing Cai,Jingjing Cai,Xiao-Jing Zhang,Peng Zhang,Zhi-Gang She,Feng Wan,Hongliang Li +8 more
TL;DR: In this paper, the authors cover recent discoveries in new targets and molecules for antifibrotic treatment, which target pathways intertwined with the fibrogenesis process, including lipid metabolism, inflammation, cell apoptosis, oxidative stress, and extracellular matrix formation.
References
More filters
Journal ArticleDOI
Salmon provides fast and bias-aware quantification of transcript expression
TL;DR: Salmon is the first transcriptome-wide quantifier to correct for fragment GC-content bias, which substantially improves the accuracy of abundance estimates and the sensitivity of subsequent differential expression analysis.
Journal ArticleDOI
Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets
Evan Z. Macosko,Evan Z. Macosko,Anindita Basu,Anindita Basu,Rahul Satija,Rahul Satija,James Nemesh,James Nemesh,Karthik Shekhar,Melissa Goldman,Melissa Goldman,Itay Tirosh,Allison R. Bialas,Nolan Kamitaki,Nolan Kamitaki,Emily M. Martersteck,John J. Trombetta,David A. Weitz,Joshua R. Sanes,Alex K. Shalek,Alex K. Shalek,Alex K. Shalek,Aviv Regev,Aviv Regev,Aviv Regev,Steven A. McCarroll,Steven A. McCarroll +26 more
TL;DR: Drop-seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution by separating them into nanoliter-sized aqueous droplets, associating a different barcode with each cell's RNAs, and sequencing them all together.
Journal ArticleDOI
Mechanisms of NAFLD development and therapeutic strategies
TL;DR: Understanding of pathogenic mechanisms and clinical features of NAFLD is driving progress in therapeutic strategies now in clinical trials and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression are discussed.
Journal ArticleDOI
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
Jorge Henao-Mejia,Eran Elinav,Chengcheng Jin,Liming Hao,Wajahat Z. Mehal,Till Strowig,Christoph A. Thaiss,Andrew L. Kau,Stephanie C. Eisenbarth,Michael J. Jurczak,Joao Paulo Camporez,Gerald I. Shulman,Gerald I. Shulman,Jeffrey I. Gordon,Hal M. Hoffman,Richard A. Flavell,Richard A. Flavell +16 more
TL;DR: Altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders.
Journal ArticleDOI
Molecular mediators of hepatic steatosis and liver injury
TL;DR: Recent advances in the understanding of the molecular events contributing to hepatic steatosis and nonalcoholic steatohepatitis are highlighted.