Over 50 billion cells undergo apoptosis each day in an adult human to maintain immune homeostasis. Hydrogen sulfide (HS) is also required to safeguard the function of immune response. However, it is unknown whether apoptosis regulates HS production. Here, we show that apoptosis-deficient MRL/ (B6.MRL-Faslpr/J) and Bim (B6.129S1-Bcl2l11tm1.1Ast/J) mice exhibit significantly reduced HS levels along with aberrant differentiation of Th17 cells, which can be rescued by the additional HS. Moreover, apoptotic cells and vesicles (apoVs) express key HS-generating enzymes and generate a significant amount of HS, indicating that apoptotic metabolism is an important source of HS. Mechanistically, HS 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 HS homeostasis and the unique role of HS in regulating Th17 cell differentiation via sulfhydration of Sep15.

中文翻译：

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细胞凋亡释放硫化氢抑制Th17细胞分化

成年人每天有超过 500 亿个细胞发生凋亡，以维持免疫稳态。硫化氢 (HS) 也是保护免疫反应功能所必需的。然而，细胞凋亡是否调节 HS 的产生尚不清楚。在这里，我们发现凋亡缺陷的 MRL/ (B6.MRL-Faslpr/J) 和 Bim (B6.129S1-Bcl2l11tm1.1Ast/J) 小鼠表现出 HS 水平显着降低以及 Th17 细胞的异常分化，这是可以挽救的通过附加 HS。此外，凋亡细胞和囊泡（apoV）表达关键的HS生成酶并产生大量HS，表明凋亡代谢是HS的重要来源。从机制上讲，HS 硫化物与硒蛋白 F (Sep15) 结合，促进信号转导子和转录激活子 1 (STAT1) 磷酸化并抑制 STAT3 磷酸化，从而抑制 Th17 细胞分化。综上所述，这项研究揭示了细胞凋亡在维持 HS 稳态中以前未知的作用，以及 HS 通过 Sep15 的硫酸化作用调节 Th17 细胞分化的独特作用。