Mus musculus Transcriptome or Gene expression. Mus musculus

Farnesoid X Receptor (FXR) activity is severely compromised in inflammatory bowel diseases (IBDs). Here we show that intestinal activation of FXR using the small molecule FexD is protective in an inflammation-driven mouse model of IBD, largely through a reduction in pro-inflammatory cytokines including IL17 and IL6. Surprisingly, Fxr was essentially undetectable in naïve and activated T cells. In contrast, FexD altered gene expression in innate lymphoid cells (ILCs), most notably a marked reduction of Il17 expression. Single cell analyses of ileal lamina propria revealed increased ILCs in the inflamed state, including a disproportionate increase in the ILC3 population. Prophylactic treatment with FexD not only decreased the proportion of ILC3s, but blocked the inflammation-driven induction of IL17A and IL17F. Furthermore, the increased ILCx-like population upon FexD treatment implicates FXR in the maturation/differentiation of infiltrating ILC precursors.