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

2 Citations (Scopus)

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
Externally publishedYes

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Interleukin-17
Ubiquitination
Fibrosis
Myofibroblasts
Gene Expression
Collagen Type I
Inflammatory Bowel Diseases
Small Interfering RNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5. / Paul, J.; Singh, A. K.; Kathania, M.; Elviche, T. L.; Zeng, M.; Basrur, V.; Theiss, A. L.; Venuprasad, K.

In: Mucosal Immunology, Vol. 11, No. 2, 01.03.2018, p. 427-436.

Research output: Contribution to journalArticle

Paul, J, Singh, AK, Kathania, M, Elviche, TL, Zeng, M, Basrur, V, Theiss, AL & Venuprasad, K 2018, 'IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5', Mucosal Immunology, vol. 11, no. 2, pp. 427-436. https://doi.org/10.1038/mi.2017.53
Paul J, Singh AK, Kathania M, Elviche TL, Zeng M, Basrur V et al. IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5. Mucosal Immunology. 2018 Mar 1;11(2):427-436. https://doi.org/10.1038/mi.2017.53
Paul, J. ; Singh, A. K. ; Kathania, M. ; Elviche, T. L. ; Zeng, M. ; Basrur, V. ; Theiss, A. L. ; Venuprasad, K. / IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5. In: Mucosal Immunology. 2018 ; Vol. 11, No. 2. pp. 427-436.
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AU - Theiss, A. L.

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