Bibliographic Details
| Title: |
OLFM4 modulates intestinal inflammation by promoting IL-22+ILC3 in the gut |
| Authors: |
Zhe Xing, Xinyao Li, Junyu He, Yimin Chen, Lei Zhu, Xiaogang Zhang, Zhengcong Huang, Jian Tang, Yuxiong Guo, Yumei He |
| Source: |
Communications Biology, Vol 7, Iss 1, Pp 1-17 (2024) |
| Publisher Information: |
Nature Portfolio, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
Biology (General), QH301-705.5 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2399-3642 |
| Relation: |
https://doaj.org/toc/2399-3642 |
| DOI: |
10.1038/s42003-024-06601-y |
| Access URL: |
https://doaj.org/article/d474516f34974f8190851e50d97e58d4 |
| Accession Number: |
edsdoj.474516f34974f8190851e50d97e58d4 |
| Database: |
Directory of Open Access Journals |
