Journal article
Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells
- Abstract:
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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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.6MB, Terms of use)
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- Publisher copy:
- 10.1016/j.jaci.2013.10.056
Authors
- Funder identifier:
- https://ror.org/03x94j517
- Funding agency for:
- Ogg, G
- Funder identifier:
- https://ror.org/029chgv08
- Funding agency for:
- Klenerman, P
- Funder identifier:
- https://ror.org/02caz1f24
- Funding agency for:
- Klenerman, P
- Xue, L
- Ogg, G
- Funder identifier:
- https://ror.org/0187kwz08
- Funding agency for:
- Ogg, G
- Publisher:
- Elsevier
- Journal:
- Journal of Allergy and Clinical Immunology More from this journal
- Volume:
- 133
- Issue:
- 4
- Pages:
- 1184-1194.e7
- Publication date:
- 2013-12-31
- Acceptance date:
- 2013-10-28
- DOI:
- EISSN:
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1097-6825
- ISSN:
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0091-6749
- Language:
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English
- Keywords:
- Pubs id:
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pubs:462662
- UUID:
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uuid:5882c732-0862-474b-845c-b0f41bf292ba
- Local pid:
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pubs:462662
- Source identifiers:
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462662
- Deposit date:
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2014-07-11
- ARK identifier:
Terms of use
- Copyright holder:
- Xue et al
- Copyright date:
- 2013
- Rights statement:
- © 2013 The Authors. Published by Elsevier Inc. Open access under CC BY-NC-ND license.
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