| First Author | Kathania M | Year | 2016 |
| Journal | Nat Immunol | Volume | 17 |
| Issue | 8 | Pages | 997-1004 |
| PubMed ID | 27322655 | Mgi Jnum | J:290010 |
| Mgi Id | MGI:6441104 | Doi | 10.1038/ni.3488 |
| Citation | Kathania M, et al. (2016) Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-gammat ubiquitination. Nat Immunol 17(8):997-1004 |
| abstractText | 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 TH17 subset of helper T cells, innate lymphoid cells and gammadelta T cells resulted in the production of elevated amounts of IL-17 in the colonic mucosa. Mechanistically, Itch bound to the transcription factor ROR-gammat and targeted ROR-gammat for ubiquitination. Inhibition or genetic inactivation of ROR-gammat 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. |
