Prostaglandin D<inf>2</inf>activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on T<inf>H</inf>2 cells
Xue L., Salimi M., Panse I., Mjösberg JM., McKenzie ANJ., Spits H., Klenerman P., Ogg G.
Background Activation of the group 2 innate lymphoid cell (ILC2) population leads to production of the classical type 2 cytokines, thus promoting type 2 immunity. Chemoattractant receptor-homologous molecule expressed on T H 2 cells (CRTH2), a receptor for prostaglandin D 2 (PGD 2 ), is expressed by human ILC2s. However, the function of CRTH2 in these cells is unclear. Objectives We sought to determine the role of PGD 2 and CRTH2 in human ILC2s and compare it with that of the established ILC2 activators IL-25 and IL-33. Methods The effects of PGD 2 , IL-25, and IL-33 on the cell migration, cytokine production, gene regulation, and receptor expression of ILC2s were measured with chemotaxis, ELISA, Luminex, flow cytometry, quantitative RT-PCR, and QuantiGene assays. The effects of PGD 2 under physiologic conditions were evaluated by using the supernatant from activated mast cells. Results PGD 2 binding to CRTH2 induced ILC2 migration and production of type 2 cytokines and many other cytokines. ILC2 activation through CRTH2 also upregulated the expression of IL-33 and IL-25 receptor subunits (ST2 and IL-17RA). The effects of PGD 2 on ILC2s could be mimicked by the supernatant from activated human mast cells and inhibited by a CRTH2 antagonist. Conclusions PGD 2 is an important and potent activator of ILC2s through CRTH2 mediating strong proallergic inflammatory responses. Through IgE-mediated mast cell degranulation, these innate cells can also contribute to adaptive type 2 immunity; thus CRTH2 bridges the innate and adaptive pathways in human ILC2s. © 2013 American Academy of Allergy, Asthma & Immunology.