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

Identification of liver‐specific CD24 + invariant NK T cells with low granzyme B production and high proliferative capacity
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鉴定具有低颗粒酶 B 产量和高增殖能力的肝脏特异性 CD24 不变 NK T 细胞

DOI:
10.1002/jlb.1a0621-309r
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发表时间:
2022
影响因子:
5.5
通讯作者:
Li Bai
Li Bai
中科院分区:
医学3区
文献类型:
--
作者:
Xiang Li;Chen Jin;Qi Chen;Xihua Zheng;Di Xie;Qielan Wu;Lu Wang;Shiyu Bai;Huimin Zhang;Li Bai

文献摘要

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不变NK T细胞(INKT)是一种天然的类淋巴细胞,能识别MHC I类分子CD1d呈递的脂类抗原。INKT细胞亚群的不同组织分布意味着这些亚群对其相关组织的区域免疫做出了贡献。INKT细胞在肝脏中丰富,肝脏是一个具有独特免疫学特性的器官。肝脏特异性iNKT细胞是否存在并致力于肝脏免疫仍是个未知数。图中显示了肝脏特异性CD24+iNKT亚群。与CD24-iNKT细胞相比,肝CD24+iNKT细胞表现出更高的增殖、葡萄糖代谢和mTOR活性。虽然肝脏中CD24+iNKT细胞和CD24-iNKT细胞产生的细胞因子数量相似,但肝脏CD24+iNKT细胞颗粒酶B的产生较低。这些肝脏特异的CD24+iNKT细胞来源于胸腺,在肝脏微环境中分化为CD24+iNKT。此外,肝脏微环境也可诱导CD24+常规T细胞的形成,与CD24-T细胞相比,这些细胞表现出更高的增殖能力和更低的颗粒酶B的产生。结果提示,肝脏微环境可能诱导肝脏特异性iNKT亚群的产生,这可能在维持肝脏动态平衡方面发挥重要作用。
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.