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

doi:10.1016/j.cmet.2023.11.012

Apoptosis releases hydrogen sulfide to inhibit Th17 cell differentiation

Cell Metab. 2024 Jan 2;36(1):78-89.e5. doi: 10.1016/j.cmet.2023.11.012. Epub 2023 Dec 18.

Authors

Qianmin Ou¹, Xinhua Qiao², Zhengshi Li¹, Luhan Niu¹, Fangcao Lei¹, Ruifeng Cheng³, Ting Xie², Ning Yang⁴, Yao Liu⁴, Ling Fu³, Jing Yang³, Xueli Mao¹, Xiaoxing Kou⁵, Chang Chen⁶, Songtao Shi⁷

Affiliations

¹ South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, China.
² National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
³ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 100101, China.
⁴ Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang 110002, China.
⁵ South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, China; Key Laboratory of Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou 510080, China.
⁶ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: changchen@ibp.ac.cn.
⁷ South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, China; Key Laboratory of Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou 510080, China. Electronic address: shisongtao@mail.sysu.edu.cn.

PMID: 38113886
DOI: 10.1016/j.cmet.2023.11.012

Abstract

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 Sep15^C38.

Keywords: SLE; Th17 cells; apoVs; apoptosis; apoptotic vesicles; hydrogen sulfide; systemic lupus erythematosus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Apoptosis
Cell Differentiation
Humans
Hydrogen Sulfide* / metabolism
Hydrogen Sulfide* / pharmacology
Mice
Mice, Inbred MRL lpr
Th17 Cells

Substances

Hydrogen Sulfide