Driving IL-17⁺ γδ T-cell migration in allergic reactions: a new "inflammatory" role for the "homeostatic" chemokine CCL25.

Chemokines are traditionally classified as homeostatic or inflammatory depending on whether they direct leukocyte migration in the absence or presence of inflammatory stimuli. CC chemokine ligand (CCL)25, a ligand for CC chemokine receptor (CCR)9, has mostly been characterized as a homeostatic chemokine that determines the migration pathway of T-cell progenitors within the thymus, and the recruitment of various lymphocyte subsets to the intestinal mucosa. In this issue of the European Journal of Immunology, Costa et al. [Eur. J. Immunol. 2012. 42: 1250-1260] describe a new inflammatory role for CCL25/CCR9 in controlling the migration of a subset of γδ T cells committed to IL-17 production (γδ17 cells) in a model of allergic pleurisy. Interestingly, the effect of CCL25 was selective for γδ17 cells, as it did not extend to other γδ or αβ T-cell subsets, and resulted in a specific increase of IL-17 (but not IL-4 or IFN-γ) levels in the allergic pleura. In this commentary, I discuss these results in the context of chemokine-mediated recruitment of γδ T cells to inflammatory sites, and the as yet unclear and controversial role of IL-17 in allergic reactions.