Details

Autor(en) / Beteiligte

• Fu, Jia-Yao
• Huang, Shi-Jia
• Wang, Bao-Li
• Yin, Jun-Hao
• Chen, Chang-Yu
• Xu, Jia-Bao
• Chen, Yan-Lin
• Xu, Shuo
• Dong, Ting
• Zhou, Hao-Nan
• Ma, Xin-Yi
• Pu, Yi-Ping
• Li, Hui
• Yang, Xiu-Juan
• Xie, Li-Song
• Wang, Zhi-Jun
• Luo, Qi
• Shao, Yan-Xiong
• Ye, Lei
• Zong, Zi-Rui
• Wei, Xin-Di
• Xiao, Wan-Wen
• Niu, Shu-Tong
• Liu, Yi-Ming
• Xu, He-Ping
• Yu, Chuang-Qi
• Duan, Sheng-Zhong
• Zheng, Ling-Yan

Titel

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

Ist Teil von

• Cell metabolism, 2024-03, Vol.36 (3), p.557-574.e10

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •KAT6A deficiency in CD4+ T cells dampens the CD4+ T cell response in autoimmunity•KAT6A supports glucose metabolism and subsequent CD4+ T cell responses•KAT6A epigenetically programs the transcriptional activity of several glycolytic genes•Inhibition of KAT6A shows promising therapeutic potential for autoimmune diseases Fu et al. report that the acetyltransferase KAT6A is relevant to CD4+ T cell response and its associated autoimmunity. Mechanistically, KAT6A epigenetically orchestrated the metabolic reprogramming of glycolytic genes, thereby supporting the proliferation and differentiation of CD4+ T cells. Genetic ablation or pharmacological inhibition of KAT6A protected mice from autoimmunity.