2. Academic Validation
  3. EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death

EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death

  • Nat Commun. 2024 Feb 12;15(1):1282. doi: 10.1038/s41467-024-45539-x.
Jiacheng Wu # 1,  Xiaoqing Xu # 1,  Jiaqi Duan 1,  Yangyang Chai 1,  Jiaying Song 1,  Dongsheng Gong 1,  Bingjing Wang 1,  Ye Hu 1 2,  Taotao Han 3,  Yuanyuan Ding 1 4,  Yin Liu 1,  Jingnan Li 5,  Xuetao Cao 6 7
Affiliations

Affiliations

  • 1 Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China.
  • 2 Frontier Research Center for Cell Response, Institute of Immunology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
  • 3 Department of Gastroenterology, Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
  • 4 Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, 215123, China.
  • 5 Department of Gastroenterology, Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China. [email protected].
  • 6 Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. [email protected].
  • 7 Frontier Research Center for Cell Response, Institute of Immunology, College of Life Sciences, Nankai University, Tianjin, 300071, China. [email protected].
  • # Contributed equally.
PMID: 38346956 DOI: 10.1038/s41467-024-45539-x
Abstract

TNF acts as one pathogenic driver for inducing intestinal epithelial cell (IEC) death and substantial intestinal inflammation. How the IEC death is regulated to physiologically prevent intestinal inflammation needs further investigation. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects intestinal epithelium from TNF-induced IEC Apoptosis. EFHD2 inhibits TNF-induced Apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin and suppresses Cofilin phosphorylation, thus blocking TNF Receptor I (TNFR1) internalization to inhibit IEC Apoptosis and consequently protecting intestine from inflammation. Our findings deepen the understanding of EFHD2 as the key regulator of membrane receptor trafficking, providing insight into death receptor signals and autoinflammatory diseases.

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Products
  • Cat. No.
    Product Name
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    Target
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  • HY-15518
    99.91%, IAP Inhibitor
    IAP