| Autor: |
Zhe Xing, Xinyao Li, Junyu He, Yimin Chen, Lei Zhu, Xiaogang Zhang, Zhengcong Huang, Jian Tang, Yuxiong Guo, Yumei He |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Communications Biology, Vol 7, Iss 1, Pp 1-17 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2399-3642 |
| DOI: |
10.1038/s42003-024-06601-y |
| Popis: |
Abstract Group 3 innate lymphoid cells (ILC3s) play key roles in intestinal inflammation. Olfactomedin 4 (OLFM4) is highly expressed in the colon and has a potential role in dextran sodium sulfate-induced colitis. However, the detailed mechanisms underlying the effects of OLFM4 on ILC3-mediated colitis remain unclear. In this study, we identify OLFM4 as a positive regulator of IL-22+ILC3. OLFM4 expression in colonic ILC3s increases substantially during intestinal inflammation in humans and mice. Compared to littermate controls, OLFM4-deficient (OLFM4−/−) mice are more susceptible to bacterial infection and display greater resistance to anti-CD40 induced innate colitis, together with impaired IL-22 production by ILC3, and ILC3s from OLFM4−/−mice are defective in pathogen resistance. Besides, mice with OLFM4 deficiency in the RORγt compartment exhibit the same trend as in OLFM4−/−mice, including colonic inflammation and IL-22 production. Mechanistically, the decrease in IL-22+ILC3 caused by OLFM4 deficiency involves the apoptosis signal-regulating kinase 1 (ASK1)- p38 MAPK signaling-dependent downregulation of RAR-related orphan receptor gamma (RORγt) protein. The OLFM4-metadherin (MTDH) complex upregulates p38/RORγt signaling, which is necessary for IL-22+ILC3 activation. The findings indicate that OLFM4 is a novel regulator of IL-22+ILC3 and essential for modulating intestinal inflammation and tissue homeostasis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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