Researcher identifies how Itch protein inhibits colonic inflammation and carcinogenesis

Venuprasad Poojary, PhD, an associate investigator at Baylor Institute for Immunology Research (BIIR), part of Baylor Scott & White Research Institute, reported this week in the journal Nature Immunology the role of a key protein in the regulatory pathway that is involved in limiting colon inflammation and tumor growth. The paper, titled "Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-gt ubiquitination," is available online in advance of the print edition.

Dr. Poojary focused on how the ubiquitin ligase protein, referred to as Itch, controls colonic inflammation. Inflammation is a protective response to microbial infection and tissue injury. However, uncontrolled inflammation is a major risk factor for the development and growth of colon cancer, which is the main cause of cancer-related deaths in the US. Uncontrolled expression of interleukin 17 (IL-17), an inflammatory growth cell, in the intestinal mucous membrane is associated with inflammation and colon cancer. However, the mechanisms by which IL-17 production is regulated remain unclear.

"We found that deficiency in the Itch protein led to spontaneous colitis and increased susceptibility to colon cancer. Our biochemical analysis revealed that Itch targets ROR-gt (a protein that induces IL-17 expression) for degradation, which reduces intestinal inflammation and inhibits colon cancer growth. Thus, we have discovered a novel regulatory mechanism that inhibits colonic inflammation and carcinogenesis," Dr. Poojary said.

Chronic inflammation can lead to inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis, which greatly reduce the quality of life of patients. IBD patients also are at high risk of developing colon cancer. Further supporting the role of Itch and the regulation of IL-17, patients with stage I/II colon cancer who have high levels of IL-17 are much less likely to have disease-free survival. According to Dr. Poojary, the new findings will lead to specific targeted therapies and their direct delivery to the site of inflammation in IBDs and colon cancer.