Cell Metabolism, 18 December, 2023, DOI：https://doi.org/10.1016/j.cmet.2023.11.012
Apoptosis releases hydrogen sulfide to inhibit Th17 cell differentiation
Qianmin Ou, Xinhua Qiao, Zhengshi Li, Luhan Niu, Fangcao Lei, Ruifeng Cheng, Ting Xie, Ning Yang, Yao Liu, Ling Fu, Jing Yang, Xueli Mao, Xiaoxing Kou, Chang Chen, Songtao Shi
Over 50 billion cells undergo apoptosis each day in an adult human to maintain immune homeostasis. Hydrogen sulfide (H2S) is also required to safeguard the function of immune response. However, it is unknown whether apoptosis regulates H2S production. Here, we show that apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) and Bim−/− (B6.129S1-Bcl2l11tm1.1Ast/J) mice exhibit significantly reduced H2S levels along with aberrant differentiation of Th17 cells, which can be rescued by the additional H2S. Moreover, apoptotic cells and vesicles (apoVs) express key H2S-generating enzymes and generate a significant amount of H2S, indicating that apoptotic metabolism is an important source of H2S. Mechanistically, H2S sulfhydrates selenoprotein F (Sep15) to promote signal transducer and activator of transcription 1 (STAT1) phosphorylation and suppress STAT3 phosphorylation, leading to the inhibition of Th17 cell differentiation. Taken together, this study reveals a previously unknown role of apoptosis in maintaining H2S homeostasis and the unique role of H2S in regulating Th17 cell differentiation via sulfhydration of Sep15C38.