Lysine acetyltransferase 6A maintains CD4 + T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity.

Autor:	Fu JY; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Huang SJ; Laboratory of Oral Microbiota and Systematic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Wang BL; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Yin JH; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Chen CY; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Xu JB; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Chen YL; Laboratory of Oral Microbiota and Systematic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China; Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Xu S; Laboratory of Oral Microbiota and Systematic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China; Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou 310000, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Dong T; Laboratory of Oral Microbiota and Systematic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Zhou HN; College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China., Ma XY; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Pu YP; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Li H; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Yang XJ; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Xie LS; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Wang ZJ; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Luo Q; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Shao YX; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Ye L; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Zong ZR; College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China., Wei XD; College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China., Xiao WW; College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China., Niu ST; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Liu YM; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Xu HP; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Science, Westlake University, Hangzhou 310024, China., Yu CQ; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China., Duan SZ; Laboratory of Oral Microbiota and Systematic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China; Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou 310000, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China. Electronic address: duansz2008@hotmail.com., Zheng LY; Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; National Center for Stomatology & National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200001, China. Electronic address: zhenglingyan@sjtu.edu.cn.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2024 Mar 05; Vol. 36 (3), pp. 557-574.e10. Date of Electronic Publication: 2024 Jan 17.
DOI:	10.1016/j.cmet.2023.12.016
Abstrakt:	Augmented CD4 + T cell response in autoimmunity is characterized by extensive metabolic reprogramming. However, the epigenetic molecule that drives the metabolic adaptation of CD4 + T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A), an epigenetic modulator that is clinically associated with autoimmunity, orchestrates the metabolic reprogramming of glucose in CD4 + T cells. KAT6A is required for the proliferation and differentiation of proinflammatory CD4 + T cell subsets in vitro, and mice with KAT6A-deficient CD4 + T cells are less susceptible to experimental autoimmune encephalomyelitis and colitis. Mechanistically, KAT6A orchestrates the abundance of histone acetylation at the chromatin where several glycolytic genes are located, thus affecting glucose metabolic reprogramming and subsequent CD4 + T cell responses. Treatment with KAT6A small-molecule inhibitors in mouse models shows high therapeutic value for targeting KAT6A in autoimmunity. Our study provides novel insights into the epigenetic programming of immunometabolism and suggests potential therapeutic targets for patients with autoimmunity. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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