IL-33 is produced by colon fibroblasts and differentially regulated in acute and chronic murine colitis
Abstract 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...
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Autores principales: | , , , |
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Formato: | article |
Lenguaje: | EN |
Publicado: |
Nature Portfolio
2021
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Materias: | |
Acceso en línea: | https://doaj.org/article/9ba6bf1031684756b61c33a2778032d4 |
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Sumario: | Abstract 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+CD90hi 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 CD90hiCD74+ 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. |
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