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Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
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YOD1 sustains NOD2-mediated protective signaling in colitis by stabilizing RIPK2
Jiangyun Shen1, Liyan Lou1, Xue Du1
1Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health); School of Pharmaceutical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
EMBO Reports
|September 27, 2024
Summary
Yeast gene YOD1 (YOD1) deficiency increases susceptibility to inflammatory bowel disease (IBD). YOD1 protects against colitis by enhancing NOD2 signaling in macrophages.
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- Inflammatory bowel disease (IBD) involves chronic gastrointestinal inflammation with unclear mechanisms.
- Yeast gene YOD1 (YOD1), a deubiquitinating enzyme, has a potential role in immune regulation.
Purpose of the Study:
- To investigate the role of YOD1 in dextran sulfate sodium (DSS)-induced colitis.
- To elucidate the molecular mechanisms by which YOD1 regulates inflammation in IBD.
Main Methods:
- Mice deficient in YOD1 were subjected to DSS-induced colitis.
- Bone marrow transplantation was performed to determine the cell-specific role of YOD1.
- Macrophage activation and signaling pathways, including NOD2/RIPK2, were analyzed.
- YOD1 expression was examined in patient samples.
Main Results:
- YOD1-deficient mice exhibited heightened susceptibility to DSS colitis.
- YOD1 derived from hematopoietic cells was found to inhibit DSS colitis.
- YOD1 promotes nucleotide-binding oligomerization domain 2 (NOD2)-mediated inflammation in macrophages by stabilizing receptor-interacting serine/threonine kinase 2 (RIPK2).
- YOD1 deficiency abrogated the protective effects of a NOD2 ligand in experimental colitis.
- YOD1 was upregulated in macrophages infiltrating the colons of colitis patients.
Conclusions:
- YOD1 is a novel regulator of colitis, acting through the NOD2 signaling pathway.
- YOD1 plays a protective role in IBD by enhancing macrophage inflammatory responses.
- Targeting YOD1 may offer a therapeutic strategy for inflammatory bowel disease.
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