Sensing of Liver‐Derived Nicotinamide by Intestinal Group 2 Innate Lymphoid Cells Links Liver Cirrhosis and Ulcerative Colitis Susceptibility
The correlation between liver disease and the progression of ulcerative colitis (UC) has remained elusive. In this study, it demonstrates that liver injury is intricately linked to the heightened severity of UC in patients, and causes more profound intestinal damage during DSS-induced colitis in mice. Metabolomics analysis of plasma from liver cirrhosis patients shows liver injury compromising nicotinamide supply for NAD<sup>+</sup> biosynthesis in the intestine. Subsequent investigation identifies intestinal group 2 innate lymphoid cells (ILC2s) are responsible for liver injury-exacerbated colitis. Reconstitution of ILC2s or the restoration of NAD<sup>+</sup> metabolism proves effective in relieving liver injury-aggravated experimental colitis. Mechanistically, the NAD<sup>+</sup> salvage pathway regulates gut ILC2s in a cell-intrinsic manner by supporting the generation of succinate, which fuels the electron transport chain to sustaining ILC2s function. This research deepens the understanding of cellular and molecular mechanisms in liver disease-UC interplay, identifying a metabolic target for innovative treatments in liver injury-complicated colitis.
Authors
- Yanyan Cui (ORCID: https://orcid.org/0000-0001-6634-9131)
- Guanjun Kou
- Yunjiao Zhai
- Xiaohuan Guo (ORCID: https://orcid.org/0000-0001-5152-3010)
- Mengqi Zheng
- Ju Qiu (ORCID: https://orcid.org/0000-0002-1543-5678)
- Ran He (ORCID: https://orcid.org/0000-0001-5002-0411)
- Chunyang Li (ORCID: https://orcid.org/0000-0002-1151-4897)
- Peng Zhang (ORCID: https://orcid.org/0000-0002-1619-903X)
- Chunhong Ma (ORCID: https://orcid.org/0000-0002-8121-4718)
- Yanqing Li (ORCID: https://orcid.org/0000-0003-0575-0399)
- Xiaoyu Liu (ORCID: https://orcid.org/0000-0002-6528-0213)
- Weijia Li (ORCID: https://orcid.org/0009-0009-2064-3437)
- Shiyang Li (ORCID: https://orcid.org/0000-0003-1487-4991)
- Lixiang Li (ORCID: https://orcid.org/0000-0001-9949-8731)
- Detian Yuan
- Jing Shen (ORCID: https://orcid.org/0000-0001-5996-7708)
- Xiuli Zuo (ORCID: https://orcid.org/0000-0002-2942-1744)
- Bowen Xu (ORCID: https://orcid.org/0000-0001-5190-8324)
- Yatai Chen (ORCID: https://orcid.org/0009-0002-1469-4771)
- TIAN Wen-Yu
- Qiuheng Tian (ORCID: https://orcid.org/0009-0005-9853-0417)
- Zhen LI
Institutions
- Shandong University (CN)
- National Clinical Research Center for Digestive Diseases (CN)
- Shanghai Institute of Nutrition and Health (CN)
- Qilu Hospital of Shandong University (CN)
- University of Chinese Academy of Sciences (CN)
- Huazhong University of Science and Technology (CN)
- Tsinghua University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2024-08-09
- DOI
- https://doi.org/10.1002/advs.202404274
- Citations
- 9
- Primary Topic
- IL-33, ST2, and ILC Pathways
- Type
- article
- Field-Weighted Citation Impact
- 2.16
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Shandong Province
- National Key Research and Development Program of China