Distinct populations of CD11b+ IRF4+ dendritic cells drive Th2 responses in the small intestine and colon. Mus musculus

We have identified the dendritic cell (DC) populations that are sufficient for the induction of T helper 2 (Th2) cell responses in the intestine against both live Trichuris muris worms, and inert Schistosoma mansoni eggs. Antigen-specific Th2 responses did not develop after deletion of IRF4 in DCs, yet IRF4-deficient DCs were not functionally affected. Instead, IRF4flox/flox CD11c-cre mice had fewer CD11b+ migrating DCs, and fewer DCs carrying parasite antigen from the intestine. Adoptive transfer of purified DCs from infected animals directly into intestinal afferent lymphatics enabled us to identify that CD11b+CD103+ DCs were central to the induction of Th2 responses in the small intestine, whereas CD11b+CD103- DCs were more important in the colon. Similarly, after pulsing with Schistosome egg antigen (SEA) in vitro, adoptively-transferred small intestinal or colonic DCs acquired the ability to induce SEA-specific Th2 responses. These data demonstrate a functional specialisation among intestinal DC populations in inducing Th2 responses, and elucidate the roles of IRF4 in this process. Overall design: Thoracic duct lymph was collected from C57BL/6 mesenteric lymphadenectomized (MLNx) mice for 18 hours, which allowed the collection of lymph draining intestinal DCs. CD11b+ CD103- and CD11b+CD103+ DCs were purfied by FACS and 30,000 cells of each subset (three replicates) were incubated with or without soluble Schistosoma mansoni egg antigen (SEA) for 18 hours, after which RNA extracton and microarray analysis were performed.