Apoptosis releases hydrogen sulfide to inhibit Th17 cell differentiation

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 (...

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Veröffentlicht in:Cell metabolism 2024-01, Vol.36 (1), p.78-89.e5
Hauptverfasser: Ou, Qianmin, Qiao, Xinhua, Li, Zhengshi, Niu, Luhan, Lei, Fangcao, Cheng, Ruifeng, Xie, Ting, Yang, Ning, Liu, Yao, Fu, Ling, Yang, Jing, Mao, Xueli, Kou, Xiaoxing, Chen, Chang, Shi, Songtao
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •Apoptotic cells are an important resource providing endogenous H2S•Apoptotic-cell-generated H2S maintains immune homeostasis•H2S inhibits the aberrant Th17 cell differentiation via sulfhydration of Sep15•H2S from apoptotic cells ameliorates murine systemic lupus erythematosus phenotypes H2S is an important endogenous regulator of the immune system. Ou et al. demonstrate that apoptotic cells and vesicles produce H2S to maintain immune homeostasis and inhibit Th17 cell differentiation via sulfhydration of Sep15C38.
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2023.11.012