2. Academic Validation
  3. Apoptosis releases hydrogen sulfide to inhibit Th17 cell differentiation

Apoptosis releases hydrogen sulfide to inhibit Th17 cell differentiation

  • Cell Metab. 2023 Dec 13:S1550-4131(23)00444-8. doi: 10.1016/j.cmet.2023.11.012.
Qianmin Ou 1,  Xinhua Qiao 2,  Zhengshi Li 1,  Luhan Niu 1,  Fangcao Lei 1,  Ruifeng Cheng 3,  Ting Xie 2,  Ning Yang 4,  Yao Liu 4,  Ling Fu 3,  Jing Yang 3,  Xueli Mao 1,  Xiaoxing Kou 5,  Chang Chen 6,  Songtao Shi 7
Affiliations

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 Sep15C38.

Keywords

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

Figures
Products