earticle

영어

Topical transcutaneous immunization (TCI) presents many clinical advantages, but its underlying mechanism for the induction of mucosal immunity remains unknown. TCI induced Ag-specific IgA Ab-secreting cells expressing CCR9 and CCR10 in the small intestine in a retinoic acid-dependent manner. These intestinal IgA Abs were maintained in Peyer’s patch-null mice but abolished in the Peyer’s patch- and lymph node-null mice. The mesenteric lymph node (MLN) was shown to be the site of IgA isotype class switching after TCI. Unexpectedly, langerin+CD8a- dendritic cells (DCs) emerged in the MLN after TCI; they did not migrate from the skin but rather differentiated rapidly from bone marrow precursors. Depletion of langerin+cells impaired intestinal IgA Ab responses after TCI. Antigens in the intestine transition from skin tissue through the lamina propria into the draining lymphatics, but whether or how this process controls mucosal immune responses is unclear. We demonstrate that small intestinal CX3CR1+ DCs of the lamina propria sample and process both circulatory and luminal antigens. Through cross-presentation of antigen CX3CR1+ DCs induce differentiation of IL-10 secreting CD8a/b T regulatory cells. Taken together, these findings suggest that mucosal DCs are indispensable for the induction of intestinal IgA Abs following skin immunization and that crosstalk between the skin and gut immune systems.