The prostaglandin D2 receptor chemoattractant receptor homologous molecule expressed on Th2 cells regulates accumulation of group 2 innate lymphoid cells in the inflamed lung (IRC7P.426)

Abstract

Abstract Group 2 innate lymphoid cells (ILC2s) promote type 2 immunity and inflammation, but the pathways that control ILC2 migration into inflamed tissues remain poorly understood. Here, we show that the prostaglandin D2 (PGD2) receptor chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2) regulates ILC2 accumulation in the lung in vivo. The frequency of ILC2s that expressed CRTH2 was significantly higher in healthy human and murine peripheral blood than in the lung, suggesting that regulation of CRTH2 expression might be associated with ILC2 accumulation in the lung. Consistent with this, CRTH2-expressing murine ILC2s accumulated in the lung in response to PGD2. Further, CRTH2-deficient mice exhibited reduced ILC2 accumulation and helminth-induced type 2 inflammation in the lung compared to wild-type mice. Critically, adoptive transfer of CRTH2-sufficient ILC2s restored helminth-induced pulmonary inflammation in CRTH2-deficient mice. Together, these data suggest that the PGD2-CRTH2 pathway regulates ILC2 accumulation and type 2 inflammation in the lung in vivo.