机构：[1]The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.重庆医科大学附属第一医院[2]Chongqing Key Laboratory of Ophthalmology, Chongqing, China.[3]Chongqing Eye Institute, Chongqing, China.[4]Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.[5]School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.[6]Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China.研究所眼科研究所首都医科大学附属北京同仁医院首都医科大学附属同仁医院
Dysregulation of CD4+ T cell differentiation is linked to autoimmune diseases. Metabolic reprogramming from oxidative phosphorylation to glycolysis and accumulation of lactate are involved in this process. However, the underlying mechanisms remain unclear. Our study showed that lactate-derived lactylation regulated CD4+ T cell differentiation. Lactylation levels in CD4+ T cells increased with the progression of experimental autoimmune uveitis (EAU). Inhibition of lactylation suppressed TH17 differentiation and attenuated EAU inflammation. The global lactylome revealed the landscape of lactylated sites and proteins in the CD4+ T cells of normal and EAU mice. Specifically, hyperlactylation of Ikzf1 at Lys164 promoted TH17 differentiation by directly modulating the expression of TH17-related genes, including Runx1, Tlr4, interleukin-2 (IL-2), and IL-4. Delactylation of Ikzf1 at Lys164 impaired TH17 differentiation. These findings exemplify how glycolysis regulates the site specificity of protein lactylation to promote TH17 differentiation and implicate Ikzf1 lactylation as a potential therapeutic target for autoimmune diseases.
基金：
This work was supported by the National Natural Science Foundation Project of China
(82070951 and 82271078), the National Key Clinical Specialties Construction Program of China,
the Chongqing Branch of National Clinical Research Center for Ocular Diseases, the Chongqing
Key Laboratory of Ophthalmology (CSTC, 2008CA5003), and the Program for Youth Innovation
in Future Medicine, Chongqing Medical University (W0047).
第一作者机构：[1]The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.[2]Chongqing Key Laboratory of Ophthalmology, Chongqing, China.[3]Chongqing Eye Institute, Chongqing, China.[4]Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.
通讯作者：
通讯机构：[1]The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.[2]Chongqing Key Laboratory of Ophthalmology, Chongqing, China.[3]Chongqing Eye Institute, Chongqing, China.[4]Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.[6]Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China.
推荐引用方式(GB/T 7714)：
Fan Wei,Wang Xiaotang,Zeng Shuhao,et al.Global lactylome reveals lactylation-dependent mechanisms underlying TH17 differentiation in experimental autoimmune uveitis[J].SCIENCE ADVANCES.2023,9(42):doi:10.1126/sciadv.adh4655.
APA：
Fan Wei,Wang Xiaotang,Zeng Shuhao,Li Na,Wang Guoqing...&Hou Shengping.(2023).Global lactylome reveals lactylation-dependent mechanisms underlying TH17 differentiation in experimental autoimmune uveitis.SCIENCE ADVANCES,9,(42)
MLA：
Fan Wei,et al."Global lactylome reveals lactylation-dependent mechanisms underlying TH17 differentiation in experimental autoimmune uveitis".SCIENCE ADVANCES 9..42(2023)
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