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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 TH2 cells (CRTH2), a receptor for prostaglandin D₂ (PGD₂), is expressed by human ILC2s. However, the function of CRTH2 in these cells is unclear. OBJECTIVES: We sought to determine the role of PGD₂ and CRTH2 in human ILC2s and compare it with that of the established ILC2 activators IL-25 and IL-33. METHODS: The effects of PGD₂, 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 PGD₂ under physiologic conditions were evaluated by using the supernatant from activated mast cells. RESULTS: PGD₂ 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 PGD₂ on ILC2s could be mimicked by the supernatant from activated human mast cells and inhibited by a CRTH2 antagonist. CONCLUSIONS: PGD₂ 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.

Original publication

DOI

10.1016/j.jaci.2013.10.056

Type

Journal article

Journal

J Allergy Clin Immunol

Publication Date

04/2014

Volume

133

Pages

1184 - 1194

Keywords

Group 2 innate lymphoid cell, IL-25, IL-33, PGD(2), adaptive type 2 immunity, chemoattractant receptor-homologous molecule expressed on T(H)2 cells, innate type 2 immunity, Chemotaxis, Cytokines, Dose-Response Relationship, Drug, Gene Expression Regulation, Humans, Immunophenotyping, Lymphocyte Activation, Lymphocyte Subsets, Mast Cells, Phenotype, Prostaglandin D2, Receptors, Immunologic, Receptors, Prostaglandin