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J Allergy Clin Immunol. 2014 Apr;133(4):1184-94. doi: 10.1016/j.jaci.2013.10.056. Epub 2013 Dec 31.

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

Author information

1
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.
2
Oxford NIHR Biomedical Research Centre, Translational Immunology Laboratory, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
3
Oxford NIHR Biomedical Research Centre, Translational Immunology Laboratory, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
4
Department of Medicine, Center for Infectious Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
5
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, United Kingdom.
6
Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
7
Oxford NIHR Biomedical Research Centre, Translational Immunology Laboratory, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: paul.klenerman@medawar.ox.ac.uk.

Abstract

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.

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

PMID:
24388011
PMCID:
PMC3979107
DOI:
10.1016/j.jaci.2013.10.056
[Indexed for MEDLINE]
Free PMC Article

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