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The histone demethylase Kdm6b regulates the maturation and cytotoxicity of TCRαβ+CD8αα+ intestinal intraepithelial lymphocytes.

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资源类型：
Pubmed体系：
作者：
Zhang Haohao[1,2] * ; Hu Yiming[1,2] * ; Liu Dandan[1,2] * ; Liu Zhi[1,2] ; Xie Ningxia[1] ; Liu Sanhong[3] ; Zhang Jie[2] ; Jiang Yuhang[1,2] ; Li Cuifeng[1,2] ; Wang Qi[1,2] ; Chen Xi[2] ; Ye Deji[1,2] ; Sun Donglin[1] ; Zhai Yujia[2] ; Yan Xinhui[2] ; Liu Yongzhong[4] ; Chen Charlie Degui[5] ; Huang Xingxu[1] ; Eugene Chin Y[6] ; Shi Yufang[2,6] ; Wu Baojin[7] ; Zhang Xiaoren[1,2] ;
机构： [1]Affiliated Cancer Hospital and Institute of Guangzhou Medical University Key Laboratory for Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes State Key Laboratory of Respiratory Disease, 510000, Guangzhou, China. [2]CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, China. [3]Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China. [4]State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 200032, Shanghai, China. [5]State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, China. [6]Institutes of Biology and Medical Sciences, Soochow University Medical College, 215000, Suzhou, China. [7]Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China.
出处：
DOI： 10.1038/s41418-021-00921-w
ISSN：

摘要：
Intestinal intraepithelial lymphocytes (IELs) are distributed along the length of the intestine and are considered the frontline of immune surveillance. The precise molecular mechanisms, especially epigenetic regulation, of their development and function are poorly understood. The trimethylation of histone 3 at lysine 27 (H3K27Me3) is a kind of histone modifications and associated with gene repression. Kdm6b is an epigenetic enzyme responsible for the demethylation of H3K27Me3 and thus promotes gene expression. Here we identified Kdm6b as an important intracellular regulator of small intestinal IELs. Mice genetically deficient for Kdm6b showed greatly reduced numbers of TCRαβ+CD8αα+ IELs. In the absence of Kdm6b, TCRαβ+CD8αα+ IELs exhibited increased apoptosis, disturbed maturation and a compromised capability to lyse target cells. Both IL-15 and Kdm6b-mediated demethylation of histone 3 at lysine 27 are responsible for the maturation of TCRαβ+CD8αα+ IELs through upregulating the expression of Gzmb and Fasl. In addition, Kdm6b also regulates the expression of the gut-homing molecule CCR9 by controlling H3K27Me3 level at its promoter. However, Kdm6b is dispensable for the reactivity of thymic precursors of TCRαβ+CD8αα+ IELs (IELPs) to IL-15 and TGF-β. In conclusion, we showed that Kdm6b plays critical roles in the maturation and cytotoxic function of small intestinal TCRαβ+CD8αα+ IELs.© 2021. The Author(s).

基金：
National Program on Key Research (2021YFA0804703, 2018YFA0107500), the National Natural Science Foundation of China (91949102, 91742113, 31570902, 81771752, 31370881) and the Guangzhou Key Medical Discipline Construction Project Fund.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类 | 1 区 生物学
小类 | 1 区 生化与分子生物学 2 区 细胞生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 1 区 生化与分子生物学 2 区 细胞生物学
第一作者：
第一作者机构： [1]Affiliated Cancer Hospital and Institute of Guangzhou Medical University Key Laboratory for Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes State Key Laboratory of Respiratory Disease, 510000, Guangzhou, China. [2]CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, China.
共同第一作者：
通讯作者：
通讯机构： [1]Affiliated Cancer Hospital and Institute of Guangzhou Medical University Key Laboratory for Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes State Key Laboratory of Respiratory Disease, 510000, Guangzhou, China. [2]CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, China.
推荐引用方式(GB/T 7714)：
Zhang Haohao,Hu Yiming,Liu Dandan,et al.The histone demethylase Kdm6b regulates the maturation and cytotoxicity of TCRαβ+CD8αα+ intestinal intraepithelial lymphocytes.[J].Cell death and differentiation.2022,doi:10.1038/s41418-021-00921-w.
APA：
Zhang Haohao,Hu Yiming,Liu Dandan,Liu Zhi,Xie Ningxia...&Zhang Xiaoren.(2022).The histone demethylase Kdm6b regulates the maturation and cytotoxicity of TCRαβ+CD8αα+ intestinal intraepithelial lymphocytes..Cell death and differentiation,,
MLA：
Zhang Haohao,et al."The histone demethylase Kdm6b regulates the maturation and cytotoxicity of TCRαβ+CD8αα+ intestinal intraepithelial lymphocytes.".Cell death and differentiation .(2022)

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