Myeloid-Derived IL-33 Limits the Severity of Dextran Sulfate Sodium–Induced Colitis

• DOI: 10.1016/j.ajpath.2020.11.004
• Publication Date: 2020-11-24T16:12:05Z
• Authors: Li-Yin Hung; Christopher F. Pa...; Bonnie Douglas; De’Broski R. Herbert
• Keywords: Mice, Knockout; 0301 basic medicine; Mice; 03 medical and health sciences; Dextran Sulfate; Animals; Epithelial Cells; Myeloid Cells; Intestinal Mucosa; Colitis; Interleukin-33; 3. Good health

IL-33 is an IL-1 family cytokine that signals through its cognate receptor, ST2, to regulate inflammation. Whether IL-33 serves a pathogenic or protective role during inflammatory bowel disease is controversial. Herein, two different strains of cell-specific conditionally deficient mice were used to compare the role of myeloid- versus intestinal epithelial cell-derived IL-33 during dextran sodium sulfate-induced colitis. Data show that loss of CD11c-restricted IL-33 exacerbated tissue pathology, coinciding with increased tissue Il6 levels and loss of intestinal forkhead box p3+ regulatory T cells. Surprisingly, the lack of intestinal epithelial cell-derived IL-33 had no impact on disease severity or tissue recovery. Thus, we show that myeloid-derived IL-33 functionally restrains colitic disease, whereas intestinal epithelial cell-derived IL-33 is dispensable.