Group 2 innate lymphoid cells collaborate with dendritic cells to potentiate memory Th2 cell responses.

Abstract

Abstract Rapid memory CD4+ T helper 2 (Th2) cell activation during allergic inflammation requires their recruitment into the affected tissue. Tissue-resident innate immune cells such as dendritic cells (DC) are essential for orchestrating local memory Th2 cell responses. We now know that tissue-resident group 2 innate lymphoid cells (ILC2) are an important innate source of type-2 cytokines in barrier sites. However, it is currently not known if ILC2 remain functionally important after the generation of adaptive Th2 cells. Here we demonstrate that group 2 innate lymphoid cells (ILC2) play a critical role in memory Th2 cell responses. By targeted ILC2 depletion, using ILC2-specific diphtheria toxin receptor expressing iCOS-T mice, we show a profound impairment in Th2 cell localization to the lungs and skin of sensitized mice after allergen re-challenge. Mechanistically, ILC2-derived IL-13 is critical for eliciting IRF4+CD11b+CD103− DCs to produce the Th2 cell-attracting chemokine CCL17. Consequently, the sentinel function of DCs is contingent on ILC2s for the generation of an efficient memory Th2 cell response. These results elucidate a key new innate mechanism in the regulation of the adaptive memory immune response to allergens.