IL-33 is produced by colon fibroblasts and differentially regulated in acute and chronic murine colitis

• Published in: Scientific reports Vol. 11; no. 1; pp. 9575 - 11
• Main Authors: Waddell, Amanda, Vallance, Jefferson E, Fox, Sejal, Rosen, Michael J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 05.05.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Actin; Animals; Colitis - chemically induced; Colitis - genetics; Colitis - metabolism; Colitis - pathology; Colon; Colon - metabolism; Colon - pathology; Dextran Sulfate; Disease Models, Animal; Female; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression Regulation; IL-1β; Inflammatory bowel disease; Inflammatory bowel diseases; Interleukin 1; Interleukin 1 receptors; Interleukin 10; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukin-33 - genetics; Interleukin-33 - metabolism; Male; Mice; Mice, Knockout; Smooth muscle; Ulcerative colitis; Vimentin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-89119-1

IL-33 is upregulated in ulcerative colitis and has a protective role in chemically-induced acute murine colitis. We aimed to determine whether IL-33 influences Il10 chronic colitis and its cellular source in health and during colitis. Il10 Il33 and Il10 Il33 littermates developed colitis of similar severity. Colon Il33 was induced in WT and Il10 mice exposed to DSS, but not in unchallenged Il10 mice with colitis. Il33-citrine reporter mice showed that Il33-citrine colocalized with α-smooth muscle actin myofibroblasts and vimentin fibroblasts in WT mice. Citrine CD74 CD90 inflammatory fibroblasts were increased with DSS treatment. IL-1β induced Il33 expression in colon myofibroblasts, but colon Il33 expression did not differ between DSS-treated WT and Il1r1 mice. In conclusion, deficiency of IL-33 does not alter the severity of chronic colitis in Il10 mice. Induction of Il33 upon DSS exposure in WT and Il10 mice, but not in unchallenged Il10 mice, suggests epithelial injury induces colon IL-33. Fibroblasts are the primary colonic source of IL-33 and IL-33-expressing CD90 CD74 fibroblasts are increased during DSS-induced colitis. IL-1β induces Il33 in colon myofibroblasts in vitro, but signaling through the IL-1R1 is not necessary for induction of IL-33 in DSS-induced colitis.