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Cited by 140IL-33, ST2, and ILC PathwaysAsthma and respiratory diseasesMast cells and histamine

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Prostaglandin E2 suppresses human group 2 innate lymphoid cell function

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Maric, Jovana, Ravindran, Avinash, Mazzurana, Luca, Björklund, Åsa K., Van Acker, Aline, Rao, Anna, Friberg, Danielle, Dahlén, Sven-Erik, Heinemann, Akos, Konya, Viktoria, Mjösberg, Jenny·2018·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2017.09.050PMC PMC5929462
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Abstract

Background Group 2 innate lymphoid cells (ILC2s) are involved in the initial phase of type 2 inflammation and can amplify allergic immune responses by orchestrating other type 2 immune cells. Prostaglandin (PG) E 2 is a bioactive lipid that plays protective roles in the lung, particularly during allergic inflammation. Objective We set out to investigate how PGE 2 regulates human ILC2 function. Methods The effects of PGE 2 on human ILC2 proliferation and intracellular cytokine and transcription factor expression were assessed by means of flow cytometry. Cytokine production was measured by using ELISA, and real-time quantitative PCR was performed to detect PGE 2 receptor expression. Results PGE 2 inhibited GATA-3 expression, as well as production of the type 2 cytokines IL-5 and IL-13, from human tonsillar and blood ILC2s in response to stimulation with a combination of IL-25, IL-33, thymic stromal lymphopoietin, and IL-2. Furthermore, PGE 2 downregulated the expression of IL-2 receptor α (CD25). In line with this observation, PGE 2 decreased ILC2 proliferation. These effects were mediated by the combined action of E-type prostanoid receptor (EP) 2 and EP4 receptors, which were specifically expressed on ILC2s. Conclusion Our findings reveal that PGE 2 limits ILC2 activation and propose that selective EP2 and EP4 receptor agonists might serve as a promising therapeutic approach in treating allergic diseases by suppressing ILC2 function.

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Metadata

Authors
Maric, J., Ravindran, A., Mazzurana, L., Björklund, Å. K., Van Acker, A., Rao, A., Friberg, D., Dahlén, S.-E., Heinemann, A., Konya, V., & Mjösberg, J.
Affiliations
  • Karolinska Institutet (SE)
  • Uppsala University (SE)
  • Karolinska University Hospital (SE)
  • Linköping University (SE)
Corresponding author
Mjösberg, Jenny
ORCID
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2018-05
Volume
141
Issue
5
Pages
1761-1773.e6
ISSN
0091-6749 (ISSN-L)
DOI
10.1016/j.jaci.2017.09.050
PMC
PMC5929462
OpenAlex
W2774252423
Cited by
140
References
2
Citations by year
2026: 9 · 2025: 5 · 2024: 14 · 2023: 14 · 2022: 12 · 2021: 19 · 2020: 26 · 2019: 18 · 2018: 23
FWCI
8.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
  • Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
Funders
  • Amgen
  • Eli Lilly and Company
  • AstraZeneca
  • GlaxoSmithKline
  • Sanofi
  • Teva Pharmaceutical Industries
  • Regeneron Pharmaceuticals
  • Swedish Cancer Foundation
  • Stiftelsen för Strategisk Forskning (ICA12-0023)
  • Austrian Science Fund (P 25531)
  • Cancerfonden (130396)
  • Svenska Sällskapet för Medicinsk Forskning
  • Knut och Alice Wallenbergs Stiftelse
  • Vetenskapsrådet (521-2013-2791)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
  • Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
Keywords
prostaglandin E2, ILC2, type 2 inflammation, allergic inflammation, EP2 receptor, EP4 receptor, GATA3, IL-5, IL-13, CD25, interleukin-2 receptor, IL-25, IL-33, thymic stromal lymphopoietin
MeSH terms
Cells, Cultured, Gene Expression Regulation, Humans, Immunity, Innate, Inflammation, Lymphocytes, Dinoprostone, Cytokines, Receptors, Prostaglandin E, GATA3 Transcription Factor

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