Apoptosis releases hydrogen sulfide to inhibit Th17 cell differentiation.
basic_science · Level V
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- Record sourced from PubMed, PMID 38113886.
- Also identified by DOI 10.1016/j.cmet.2023.11.012.
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Abstract
Over 50 billion cells undergo apoptosis each day in an adult human to maintain immune homeostasis. Hydrogen sulfide (H<sub>2</sub>S) is also required to safeguard the function of immune response. However, it is unknown whether apoptosis regulates H<sub>2</sub>S production. Here, we show that apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) and Bim<sup>-/-</sup> (B6.129S1-Bcl2l11tm1.1Ast/J) mice exhibit significantly reduced H<sub>2</sub>S levels along with aberrant differentiation of Th17 cells, which can be rescued by the additional H<sub>2</sub>S. Moreover, apoptotic cells and vesicles (apoVs) express key H<sub>2</sub>S-generating enzymes and generate a significant amount of H<sub>2</sub>S, indicating that apoptotic metabolism is an important source of H<sub>2</sub>S. Mechanistically, H<sub>2</sub>S 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 H<sub>2</sub>S homeostasis and the unique role of H<sub>2</sub>S in regulating Th17 cell differentiation via sulfhydration of Sep15<sup>C38</sup>.
Medical subject headings
- Hydrogen Sulfide