Fortin and colleagues grant a nameless group of dendritic cells (DCs) an identity and show that they promote Th17-mediated colitis.
Until now, some 40% of dendritic cells in the gut were characterized by the absence of the integrin CD103 on their surface. Here, the authors report that CD103− DCs express signal regulatory protein-α (SIRPα). And unlike CD103+ DCs that favor the differentiation of protective regulatory T cells, SIRPα+ DCs from intestinal lymph nodes promoted Th17 polarization both in vitro and in a mouse model of colitis. These findings are consistent with prior reports showing that CD103− DCs drive the production of IL-17 from T cells. SIRPα+ DCs from the spleen and bone marrow also elicited Th17 responses in culture, suggesting that the response isn't gut specific.
The generation of Th17 responses depended on the SIRPα+ ligand CD47. The molecule was not required to deliver a Th17-promoting signal to the T cells, as CD47 was dispensable for generating Th17 responses in culture. Instead, expression of CD47 on the DCs was needed for the cells to migrate to the intestinal lymph nodes where they prime T cells. SIRPα+ cells in other parts of the body, such as Langerhans cells in the skin, similarly rely on CD47 to migrate to local lymph nodes. How CD47 drives SIRPα+ cell migration remains unknown.
Both Th17 and Th1 responses have been reported during Crohn's disease and colitis. However, elevated levels of IL-17, IL-6, and IL-23—cytokines associated with Th17 cells—have been increasingly tied to these diseases in humans and mice.
