• J. Allergy Clin. Immunol. · Apr 2014

    Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells.

    • Luzheng Xue, Maryam Salimi, Isabel Panse, Jenny M Mjösberg, Andrew N J McKenzie, Hergen Spits, Paul Klenerman, and Graham Ogg.
    • Oxford NIHR Biomedical Research Centre, Translational Immunology Laboratory, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom. Electronic address: luzheng.xue@ndm.ox.ac.uk.
    • J. Allergy Clin. Immunol. 2014 Apr 1;133(4):1184-94.

    BackgroundActivation 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.ObjectivesWe 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.MethodsThe 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.ResultsPGD₂ 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.ConclusionsPGD₂ 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.Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved.

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