Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-γt ubiquitination

Mahesh Kathania, Prashant Khare, Minghui Zeng, Brandi Cantarel, Haiying Zhang, Hideki Ueno, K. Venuprasad

Research output: Contribution to journalArticle

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Abstract

Dysregulated expression of interleukin 17 (IL-17) in the colonic mucosa is associated with colonic inflammation and cancer. However, the cell-intrinsic molecular mechanisms by which IL-17 expression is regulated remain unclear. We found that deficiency in the ubiquitin ligase Itch led to spontaneous colitis and increased susceptibility to colon cancer. Itch deficiency in the T H 17 subset of helper T cells, innate lymphoid cells and γδ T cells resulted in the production of elevated amounts of IL-17 in the colonic mucosa. Mechanistically, Itch bound to the transcription factor ROR-γt and targeted ROR-γt for ubiquitination. Inhibition or genetic inactivation of ROR-γt attenuated IL-17 expression and reduced spontaneous colonic inflammation in Itch -/- mice. Thus, we have identified a previously unknown role for Itch in regulating IL-17-mediated colonic inflammation and carcinogenesis.

Original languageEnglish (US)
Pages (from-to)997-1004
Number of pages8
JournalNature Immunology
Volume17
Issue number8
DOIs
StatePublished - Jul 19 2016

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Interleukin-17
Ubiquitination
Colon
Carcinogenesis
Inflammation
Colonic Neoplasms
Mucous Membrane
Th17 Cells
Colitis
Ligases
Ubiquitin
Transcription Factors
Lymphocytes
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Kathania, M., Khare, P., Zeng, M., Cantarel, B., Zhang, H., Ueno, H., & Venuprasad, K. (2016). Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-γt ubiquitination. Nature Immunology, 17(8), 997-1004. https://doi.org/10.1038/ni.3488

Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-γt ubiquitination. / Kathania, Mahesh; Khare, Prashant; Zeng, Minghui; Cantarel, Brandi; Zhang, Haiying; Ueno, Hideki; Venuprasad, K.

In: Nature Immunology, Vol. 17, No. 8, 19.07.2016, p. 997-1004.

Research output: Contribution to journalArticle

Kathania, M, Khare, P, Zeng, M, Cantarel, B, Zhang, H, Ueno, H & Venuprasad, K 2016, 'Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-γt ubiquitination', Nature Immunology, vol. 17, no. 8, pp. 997-1004. https://doi.org/10.1038/ni.3488
Kathania, Mahesh ; Khare, Prashant ; Zeng, Minghui ; Cantarel, Brandi ; Zhang, Haiying ; Ueno, Hideki ; Venuprasad, K. / Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-γt ubiquitination. In: Nature Immunology. 2016 ; Vol. 17, No. 8. pp. 997-1004.
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