| First Author | Paul J | Year | 2018 |
| Journal | Mucosal Immunol | Volume | 11 |
| Issue | 2 | Pages | 427-436 |
| PubMed ID | 28612841 | Mgi Jnum | J:281778 |
| Mgi Id | MGI:6381324 | Doi | 10.1038/mi.2017.53 |
| Citation | Paul J, et al. (2018) IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5. Mucosal Immunol 11(2):427-436 |
| abstractText | 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 alpha-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. |
