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STAT3 expression in dendritic cells protects mice from colitis by a gut microbiome-dependent mechanism

Liu, J.; Szilagyi, K.; Capitano, M.; Iyer, A. K.; He, J.; Olson, M.; Du, J.; Van Der Pol, W.; Morrow, C. D.; Zhou, B.; Kaplan, M.; Dent, A. L.; Brutkiewicz, R.

2021-08-01 immunology
10.1101/2021.07.31.453520 bioRxiv
Show abstract

An imbalance in gut homeostasis results in local and systemic pathogenesis. It is still not well-understood how the immune system interacts with the gut microbiome and maintains a delicate balance. Here, we utilized a mouse model in which STAT3 expression is deleted in CD11c+ (i.e., dendritic) cells (STAT3 cKO); these mice developed an ulcerative colitis-like disease, colon carcinoma and myelodysplastic syndrome-like disease. Circulating IgE levels in STAT3 cKO mice were significantly elevated. The gut microbiome was indispensable for the observed pathogenesis, as treatment with broad-spectrum antibiotics or cross-fostering STAT3 cKO pups with mothers harboring a different microbiome prevented disease development. Gut microbiome analyses suggested that decreased commensal bacteria and increased pathogenic bacteria most likely contributed to disease. Our data suggest that STAT3 controls the manifestation of inflammation in the gut caused by the microbiome. Therefore, we conclude that a deficiency of STAT3 in DCs is sufficient to trigger uncontrolled inflammation and the development of inflammatory bowel disease.

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