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

Autor: Xue L; 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., Salimi M; 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., Panse I; Oxford NIHR Biomedical Research Centre, Translational Immunology Laboratory, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom., Mjösberg JM; Department of Medicine, Center for Infectious Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden., McKenzie AN; MRC Laboratory of Molecular Biology, Hills Road, Cambridge, United Kingdom., Spits H; Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Klenerman P; 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., Ogg G; 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.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2014 Apr; Vol. 133 (4), pp. 1184-94. Date of Electronic Publication: 2013 Dec 31.
DOI: 10.1016/j.jaci.2013.10.056
Abstrakt: 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.
(Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved.)
Databáze: MEDLINE
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