IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5

J. Paul, A. K. Singh, M. Kathania, T. L. Elviche, M. Zeng, V. Basrur, A. L. Theiss, K. Venuprasad

Research output: Contribution to journalArticle

6 Scopus citations

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 languageEnglish (US)
Pages (from-to)427-436
Number of pages10
JournalMucosal Immunology
Volume11
Issue number2
DOIs
StatePublished - Mar 1 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5'. Together they form a unique fingerprint.

  • Cite this

    Paul, J., Singh, A. K., Kathania, M., Elviche, T. L., Zeng, M., Basrur, V., Theiss, A. L., & Venuprasad, K. (2018). IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5. Mucosal Immunology, 11(2), 427-436. https://doi.org/10.1038/mi.2017.53