IL-36α expression is elevated in ulcerative colitis and promotes colonic inflammation

Area of Science:

• Immunology
• Gastroenterology
• Cytokine Signaling

Background:

• The IL-36 cytokine family is implicated in psoriasis pathogenesis.
• Mechanisms linking psoriasis and inflammatory bowel disease (IBD) suggest potential roles for IL-36 in gastrointestinal inflammation.
• No prior studies have investigated IL-36 family involvement in gastrointestinal inflammation.

Purpose of the Study:

• To investigate the role of IL-36 signaling in colonic inflammation.
• To determine if IL-36α expression is altered in ulcerative colitis.
• To evaluate the therapeutic potential of targeting the IL-36 receptor pathway in IBD.

Main Methods:

• Quantified IL-36α expression in colonic mucosa of ulcerative colitis patients and mice.
• Utilized IL-36 receptor-deficient (Il36r-/-) mice in DSS-induced colitis and Citrobacter rodentium infection models.
• Assessed disease severity, inflammatory cell infiltration, bacterial colonization, and T helper cell responses (Th17, Th1).

Main Results:

• IL-36α expression was significantly elevated in the colonic mucosa of ulcerative colitis patients and inflamed mouse colons.
• Il36r-/- mice showed reduced disease severity in DSS-induced colitis with decreased innate inflammatory cell infiltration.
• Il36r-/- mice exhibited reduced inflammatory cell recruitment and increased bacterial colonization during Citrobacter rodentium infection, alongside altered T helper cell responses (increased Th17, decreased Th1).

Conclusions:

• IL-36 signaling plays a significant role in mediating colonic inflammation.
• IL-36 receptor deficiency protects against experimental colitis and alters immune responses.
• The IL-36 receptor pathway represents a potential novel therapeutic target for IBD.