Dermal regulatory T cells display distinct migratory behavior that is modulated during adaptive and innate inflammation (650.13)

Abstract

Regulatory T cells (Tregs) are important in controlling skin inflammation, an effect dependent on their ability to home to this organ. However, little is known regarding their behavior in the skin. Here we used multiphoton imaging in Foxp3‐GFP mice to examine the behavior of endogenous Tregs in skin. While Tregs were readily detectable in the uninflamed dermis, most were non‐motile. Induction of contact sensitivity increased the proportion of motile Tregs, as well as inducing Treg recruitment. This response was significantly blunted in mice challenged with an irrelevant hapten, and by inhibition of effector cell recruitment, indicating a role for T cell‐dependent inflammation in induction of Treg migration. Moreover, induction of Treg migration was inhibited by local injection of a CCR4 antagonist, indicating a role for CCR4 in this response. Exposure of naïve mice to hapten also induced an increase in the proportion of migratory Tregs, demonstrating that innate signals can also induce Treg migration. Simultaneous examination of the migration of CD4+ effector cells and Tregs in the same region of uninflamed skin demonstrated that effector cells behaved differently, being uniformly highly migratory. These findings indicate that Treg behavior in skin differs from that of CD4+ effector cells, in that only a low proportion of Tregs are migratory under resting conditions. However, during inflammation the proportion of migratory Tregs increases, raising the possibility that this response may be important in controlling skin inflammation.