PT - JOURNAL ARTICLE AU - Lili Chen AU - Zhengxiang He AU - Alina Cornelia Iuga AU - Sebastião N. Martins Filho AU - Jeremiah J. Faith AU - Jose C. Clemente AU - Madhura Deshpande AU - Anitha Jayaprakash AU - Jean-Frederic Colombel AU - Juan J. Lafaille AU - Ravi Sachidanandam AU - Glaucia C. Furtado AU - Sergio A. Lira TI - Diet Modifies Colonic Microbiota and CD4<sup>+</sup> T cell Repertoire to Trigger Flares in a Novel Model of Colitis Induced by IL-23 AID - 10.1101/262634 DP - 2018 Jan 01 TA - bioRxiv PG - 262634 4099 - http://biorxiv.org/content/early/2018/02/08/262634.short 4100 - http://biorxiv.org/content/early/2018/02/08/262634.full AB - A wealth of experimental data points to immunological and environmental factors in the pathogenesis of inflammatory bowel disease (IBD). Here we study the role of IL-23, the microbiome, and the diet in the development of colitis. To promote IL-23 expression in vivo, we generated a mouse model in which IL-23 was conditionally expressed by CX3CR1+ myeloid cells, upon cyclic administration of tamoxifen in a specific diet (diet 2019). IL-23 expression induced an intestinal inflammatory disease that resembled ulcerative colitis in humans with cycles of acute disease and remission. The relapses were caused by the diet switch from the conventional diet used in our facility (diet 5053) to the diet 2019, and were not dependent on tamoxifen after the first cycle. The switch in the diet modified the microbiota, but did not alter the levels of IL-23. Colitis induction depended on the microbiota and required CD4 T lymphocytes. Colitis-inducing CD4+ T cells were found in the mesenteric lymph node and large intestine during remission and were able to trigger disease when transferred to lymphopenic mice, but only upon diet modification. The CD4 TCR repertoire in the diseased recipient Rag−/− mice had reduced diversity associated with the expansion of dominant T cell clones. These findings reveal a critical role for IL-23 in generation of a CD4+ T cell population in mice that is sensitive to a modification of intestinal bacterial flora subsequent to a dietary manipulation. Dietary changes occurring in the context of altered IL-23 expression may contribute to the onset and progression of IBD.