Abstract
Intestinal fibrosis is a major complication in inflammatory bowel diseases, but the regulatory mechanism that inhibits fibrosis remains unclear. Here we demonstrate that Itch -/- myofibroblasts express increased amounts of profibrotic collagen type I and α-SMA in response to IL-17. Mechanistically, we demonstrate that Itch directly binds to HIC-5 and targets it for K63-linked ubiquitination to inhibit IL-17-driven intestinal fibrosis. Reconstitution of Itch -/- myofibroblasts with wild-type Itch but not the Itch-C830A mutant normalized the expression of profibrotic genes. Similarly, shRNA-mediated inhibition of HIC-5 normalized the expression of profibrotic gene expression. Thus, we have uncovered a novel mechanism by which Itch negatively regulates intestinal fibrosis.
Original language | English (US) |
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Pages (from-to) | 427-436 |
Number of pages | 10 |
Journal | Mucosal Immunology |
Volume | 11 |
Issue number | 2 |
DOIs | |
State | Published - Mar 1 2018 |
Externally published | Yes |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology