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HOIL1 regulates group 2 innate lymphoid cell numbers and type 2 inflammation in the small intestine
- Source :
- Mucosal Immunology; 20220101, Issue: Preprints p1-14, 14p
- Publication Year :
- 2022
-
Abstract
- Patients with mutations in HOIL1experience a complex immune disorder including intestinal inflammation. To investigate the role of HOIL1in regulating intestinal inflammation, we employed a mouse model of partial HOIL1 deficiency. The ileum of HOIL1-deficient mice displayed features of type 2 inflammation including tuft cell and goblet cell hyperplasia, and elevated expression of Il13, Il5and Il25mRNA. Inflammation persisted in the absence of T and B cells, and bone marrow chimeric mice revealed a requirement for HOIL1 expression in radiation-resistant cells to regulate inflammation. Although disruption of IL-4 receptor alpha (IL4Rα) signaling on intestinal epithelial cells ameliorated tuft and goblet cell hyperplasia, expression of Il5and Il13mRNA remained elevated. KLRG1hiCD90logroup 2 innate lymphoid cells were increased independent of IL4Rα signaling, tuft cell hyperplasia and IL-25 induction. Antibiotic treatment dampened intestinal inflammation indicating commensal microbes as a contributing factor. We have identified a key role for HOIL1, a component of the Linear Ubiquitin Chain Assembly Complex, in regulating type 2 inflammation in the small intestine. Understanding the mechanism by which HOIL1 regulates type 2 inflammation will advance our understanding of intestinal homeostasis and inflammatory disorders and may lead to the identification of new targets for treatment.
Details
- Language :
- English
- ISSN :
- 19330219 and 19353456
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Mucosal Immunology
- Publication Type :
- Periodical
- Accession number :
- ejs59640069
- Full Text :
- https://doi.org/10.1038/s41385-022-00520-z