Identification of liver-specific CD24+ invariant NK T cells with low granzyme B production and high proliferative capacity

鉴定具有低颗粒酶 B 产生和高增殖能力的肝脏特异性 CD24+ 恒定 NK T 细胞

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作者:Xiang Li, Chen Jin, Qi Chen, Xihua Zheng, Di Xie, Qielan Wu, Lu Wang, Shiyu Bai, Huimin Zhang, Li Bai

Abstract

Invariant NK T (iNKT) cells are innate-like lymphocytes that can recognize the lipid Ag presented by MHC I like molecule CD1d. Distinct tissue distribution of iNKT cells subsets implies a contribution of these subsets to their related tissue regional immunity. iNKT cells are enriched in liver, an organ with unique immunological properties. Whether liver-specific iNKT cells exist and dedicate to the liver immunity remains elusive. Here, a liver-specific CD24+ iNKT subset is shown. Hepatic CD24+ iNKT cells show higher levels of proliferation, glucose metabolism, and mTOR activity comparing to CD24- iNKT cells. Although CD24+ iNKT cells and CD24- iNKT cells in the liver produce similar amounts of cytokines, the hepatic CD24+ iNKT cells exhibit lower granzyme B production. These liver-specific CD24+ iNKT cells are derived from thymus and differentiate into CD24+ iNKT in the liver microenvironment. Moreover, liver microenvironment induces the formation of CD24+ conventional T cells as well, and these cells exhibit higher proliferation ability but lower granzyme B production in comparison with CD24- T cells. The results propose that liver microenvironment might induce the generation of liver-specific iNKT subset that might play an important role in maintaining liver homeostasis.

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