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

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(hi) 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(hi)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.