journal article·2024-10Open access

Sensing of Liver‐Derived Nicotinamide by Intestinal Group 2 Innate Lymphoid Cells Links Liver Cirrhosis and Ulcerative Colitis Susceptibility

Jing Shen, Zhen Li, Xiaoyu Liu, Mengqi Zheng, Peng Zhang, Yatai Chen, Qiuheng Tian, Wenyu Tian, Guanjun Kou, Yanyan Cui, Bowen Xu, Yunjiao Zhai, Weijia Li, Xiaohuan Guo, Ju Qiu, Chunyang Li, Ran He, Lixiang Li, Chunhong Ma, Yanqing Li, Xiuli Zuo, Detian Yuan, Shiyang Li

Advanced Science· Volume 11· Issue 38

Abstract

Abstract 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+ 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+ metabolism proves effective in relieving liver injury‐aggravated experimental colitis. Mechanistically, the NAD+ 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.
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Research context

OpenAlex topics: IL-33, ST2, and ILC Pathways · Immune Cell Function and Interaction · Eosinophilic Esophagitis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Gastroenterology Qilu Hospital of Shandong University Jinan 250012 China

Advanced Medical Research Institute Shandong University Jinan 250012 China

Shandong Provincial Clinical Research Center for Digestive diseases Jinan 250012 China

Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Shandong University Jinan 250012 China

Institute for Immunology School of Medicine Tsinghua University Beijing 100084 China

Beijing Key Lab for Immunological Research on Chronic Diseases Tsinghua University Beijing 100084 China

CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 China

Key Laboratory for Experimental Teratology of Ministry of Education and Department of Histology and Embryology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 China

Department of Immunology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 43003 China

Department of Immunology School of Basic Medical Sciences Cheeloo Medical College of Shandong University Jinan 250012 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Natural Science Foundation of Shandong Province

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