Bile acid conditioned Dendritic cells through FXR and specialize T cell function in the ileum

Abstract The accumulation of locally-reabsorbed bile acids (BAs) is suggested to contribute the development terminal ileitis. Our previous data showed nuclear receptor Constitutive Androstane Receptor (CAR) can directs T cell adaptation BAs in ileum by promoting IL-10 producing Tr1 cells prevent Still, mechanisms which BA activate CAR ileal not known. As recognized as a sensor, its activation may involves indirect pathways, such dendritic (DCs). Farnesoid X (FXR), direct primary highly expressed both human and mouse DCs. Therefore, we hypothesized that BA-sensing mucosal DCs through FXR condition upregulate enforce anti-inflammatory functions. result indicated WT exposed agonist, chenodeoxycholic acid (CDCA), displayed increased production IL-23a decreased IL-6. While, CD4 +T cocultured with CDCA-treated CAR/Nr1i3, targets, cMyc MDR1. Importantly, these observations were diminished from −/−mice. In addition, when depleted DC (CD11cCreFXR fl/fl, ΔDC), migration intestine deficient, low expressions CCL19, CCR9 less CD11c +CD11b −CD103 +MHCII +migratory population mesenteric lymph nodes. Meanwhile, ΔDCmice failed promote CAR/Nr1i3as well IL10in cells. Furthermore, −/−RAG2 −/−mice developed severe ileitis after engrafted naïve cell. These results suggest specializes intestinal function ileum. Collectively, studies will shed new light on understanding treatment patients.