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- Title
Early life gut microbiota sustains liver-resident natural killer cells maturation via the butyrate-IL-18 axis.
- Authors
Tian, Panpan; Yang, Wenwen; Guo, Xiaowei; Wang, Tixiao; Tan, Siyu; Sun, Renhui; Xiao, Rong; Wang, Yuzhen; Jiao, Deyan; Xu, Yachen; Wei, Yanfei; Wu, Zhuanchang; Li, Chunyang; Gao, Lifen; Ma, Chunhong; Liang, Xiaohong
- Abstract
Liver-resident natural killer cells, a unique lymphocyte subset in liver, develop locally and play multifaceted immunological roles. However, the mechanisms for the maintenance of liver-resident natural killer cell homeostasis remain unclear. Here we show that early-life antibiotic treatment blunt functional maturation of liver-resident natural killer cells even at adulthood, which is dependent on the durative microbiota dysbiosis. Mechanistically, early-life antibiotic treatment significantly decreases butyrate level in liver, and subsequently led to defective liver-resident natural killer cell maturation in a cell-extrinsic manner. Specifically, loss of butyrate impairs IL-18 production in Kupffer cells and hepatocytes through acting on the receptor GPR109A. Disrupted IL-18/IL-18R signaling in turn suppresses the mitochondrial activity and the functional maturation of liver-resident natural killer cells. Strikingly, dietary supplementation of experimentally or clinically used Clostridium butyricum restores the impaired liver-resident natural killer cell maturation and function induced by early-life antibiotic treatment. Our findings collectively unmask a regulatory network of gut-liver axis, highlighting the importance of the early-life microbiota in the development of tissue-resident immune cells. Liver-resident natural killer cells develop locally and have multiple immunological roles in situ. Here the authors investigate the gut-liver axis and show the impact of the intestinal microbiota on the development of liver-resident natural killer cells.
- Subjects
KILLER cells; GUT microbiome; LYMPHOCYTE subsets; KUPFFER cells; CLOSTRIDIUM butyricum; HOMEOSTASIS
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-37419-7