Epithelial-derived IL-18 regulates Th17 cell differentiation and Foxp3⁺ Treg cell function in the intestine

Area of Science:

• Immunology
• Gastroenterology
• Cytokine Biology

Background:

• Elevated interleukin-18 (IL-18) levels are observed in chronic inflammatory disorders like inflammatory bowel disease (IBD).
• Polymorphisms in the IL18R1-IL18RAP locus are linked to IBD susceptibility.
• The precise role of IL-18 in regulating intestinal CD4(+) T cells remains unclear.

Purpose of the Study:

• To investigate the role of IL-18 in modulating intestinal CD4(+) T cell subsets.
• To understand IL-18's impact on T helper type 17 (Th17) and regulatory T (Treg) cells in the gut.
• To explore IL-18's contribution to intestinal homeostasis and inflammation.

Main Methods:

• Analysis of IL-18 receptor 1 (IL-18R1) expression on intestinal CD4(+) T cells.
• Investigation of IL-18's effects on Th17 cell differentiation and IL-1R1 signaling.
• Assessment of IL-18R1's necessity for Treg cell function in controlling intestinal inflammation.

Main Results:

• IL-18 receptor 1 (IL-18R1) is highly expressed on intestinal effector and regulatory CD4(+) T cells, particularly Th17 cells.
• Intestinal epithelial cells secrete IL-18, which limits colonic Th17 cell differentiation by antagonizing IL-1R1 signaling.
• IL-18R1 signaling is crucial for Treg cell-mediated control of intestinal inflammation, promoting effector molecule expression.

Conclusions:

• IL-18 is a critical epithelial-derived cytokine that differentially regulates intestinal CD4(+) T cell subsets.
• IL-18 influences both homeostatic and inflammatory processes in the intestine.
• Findings suggest IL-18 modulation as a potential therapeutic strategy for chronic inflammatory disorders.