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Peer-reviewedCC BY-NC-NDActa pharmaceutica Sinica. B

Intestinal epithelial CSE-derived H2S alleviates food allergy via modulating the IL-25/ILC2 axis

  • Zhengnan Ren1
  • Li-Long Pan2
  • Yanyan Liu3
  • He Liu3
  • Yu Ma3
  • Binbin Li1
  • Meirong Wu3
  • Wenjie Liang1
  • Haizhi Tian3
  • Jihui Zuo3
  • Xiaoliang Dong2
  • Jia Sun1
  1. 1School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
  2. 2MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China
  3. 3State Key Laboratory of Food Science and Resources and School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
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Abstract

Hydrogen sulfide (H2S), an endogenous gasotransmitter, has garnered increasing attention for its role in modulating immune responses and intestinal barrier function. In this study, diminished jejunal H2S levels and expression of its synthesizing enzyme cystathionine gamma-lyase (CSE) in intestinal epithelium were observed in ovalbumin (OVA)-induced food allergic mice. CSE deficiency aggravated OVA-induced food allergy by activating the IL-25/ILC2 axis and enhancing type 2 immune responses, effects that were reversed by exogenous H2S supplementation. Furthermore, H2S treatment suppressed intestinal epithelial cell-derived IL-25 expression by inhibiting c-Jun. IL-25 neutralization attenuated ILC2-driven type 2 immune responses and alleviated allergic symptoms in OVA-challenged CSE-knockout (Cse−/−) mice. Moreover, ILC2 inhibition diminished type 2 cytokine production and disrupted the IL-25 feedback loop, thereby ameliorating food allergy in Cse−/− mice. These findings highlight that intestinal epithelial CSE-derived H2S alleviates food allergy via the IL-25/ILC2 axis and serves as a potential therapeutic target for allergic diseases.

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Cite

BibTeXRIS
BibTeX
@article{ren2026intestinal,
  title = {{Intestinal epithelial CSE-derived H2S alleviates food allergy via modulating the IL-25/ILC2 axis}},
  author = {Zhengnan Ren and Li-Long Pan and Yanyan Liu and He Liu and Yu Ma and Binbin Li and Meirong Wu and Wenjie Liang and Haizhi Tian and Jihui Zuo and Xiaoliang Dong and Jia Sun},
  journal = {Acta pharmaceutica Sinica. B},
  year = {2026},
  month = jul,
  doi = {10.1016/j.apsb.2026.07.046},
  url = {https://europepmc.org/article/PMC/PMC13729544},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Intestinal epithelial CSE-derived H2S alleviates food allergy via modulating the IL-25/ILC2 axis
AU  - Zhengnan Ren
AU  - Li-Long Pan
AU  - Yanyan Liu
AU  - He Liu
AU  - Yu Ma
AU  - Binbin Li
AU  - Meirong Wu
AU  - Wenjie Liang
AU  - Haizhi Tian
AU  - Jihui Zuo
AU  - Xiaoliang Dong
AU  - Jia Sun
PY  - 2026
DA  - 2026/07/30
JO  - Acta pharmaceutica Sinica. B
DO  - 10.1016/j.apsb.2026.07.046
UR  - https://europepmc.org/article/PMC/PMC13729544
AB  - Hydrogen sulfide (H2S), an endogenous gasotransmitter, has garnered increasing attention for its role in modulating immune responses and intestinal barrier function. In this study, diminished jejunal H2S levels and expression of its synthesizing enzyme cystathionine gamma-lyase (CSE) in intestinal epithelium were observed in ovalbumin (OVA)-induced food allergic mice. CSE deficiency aggravated OVA-induced food allergy by activating the IL-25/ILC2 axis and enhancing type 2 immune responses, effects that were reversed by exogenous H2S supplementation. Furthermore, H2S treatment suppressed intestinal epithelial cell-derived IL-25 expression by inhibiting c-Jun. IL-25 neutralization attenuated ILC2-driven type 2 immune responses and alleviated allergic symptoms in OVA-challenged CSE-knockout (Cse−/−) mice. Moreover, ILC2 inhibition diminished type 2 cytokine production and disrupted the IL-25 feedback loop, thereby ameliorating food allergy in Cse−/− mice. These findings highlight that intestinal epithelial CSE-derived H2S alleviates food allergy via the IL-25/ILC2 axis and serves as a potential therapeutic target for allergic diseases.
SN  - 2211-3835
SN  - 2211-3843
ER  -