TLR5 mediates CD172α+ intestinal lamina propria dendritic cell induction of Th17 cells

Multiple mechanisms exist in regulation of host responses to massive challenges from microbiota to maintain immune homeostasis in the intestines. Among these is the enriched Th17 cells in the intestines, which regulates intestinal homeostasis through induction of antimicrobial peptides and secretory IgA among others. However, the means by which Th17 cells develop in response to microbiota is still not completely understood. Although both TLR5 and CD172 alpha(+) lamina propria dendritic cells (LPDC) have been shown to promote Th17 cell development, it is still unclear whether TLR5 mediates the CD172 alpha(+) LPDC induction of Th17 cells. By using a microbiota antigen-specific T cell reporter mouse system, we demonstrated that microbiota antigen-specific T cells developed into Th17 cells in the intestinal LP, but not in the spleen when transferred into TCR beta x delta(-/-) mice. LPDCs expressed high levels of TLR5, and most CD172 alpha(+) LPDCs also co-expressed TLR5. LPDCs produced high levels of IL-23, IL-6 and TGF beta when stimulated with commensal flagellin and promoted Th17 cell development when cultured with full-length CBir1 flagellin but not CBir1 peptide. Wild-type CD172 alpha(+), but not CD172 alpha(-), LPDCs induced Th17 cells, whereas TLR5-deficient LPDC did not induce Th17 cells. Our data thereby demonstrated that TLR5 mediates CD172 alpha(+) LPDC induction of Th17 cells in the intestines.