The Prostaglandin D2 Receptor CRTH2 Contributes to Airway Hyperresponsiveness during Airway Inflammation Induced by Sensitization without an Adjuvant in Mice

Satoshi Hanzawa; Makiko Sugiura; Susumu Nakae; Masahiro Masuo; Hideaki Morita; Kenji Matsumoto; Kazuyoshi Takeda; Ko Okumura; Masataka Nakamura; Tatsukuni Ohno; Yasunari Miyazaki

doi:10.1159/000537840

The Prostaglandin D2 Receptor CRTH2 Contributes to Airway Hyperresponsiveness during Airway Inflammation Induced by Sensitization without an Adjuvant in Mice

Int Arch Allergy Immunol. 2024 Apr 10:1-9. doi: 10.1159/000537840. Online ahead of print.

Authors

Satoshi Hanzawa^{1

2}, Makiko Sugiura^{1

3}, Susumu Nakae^{4

5}, Masahiro Masuo^{1

6}, Hideaki Morita^{7

8}, Kenji Matsumoto⁷, Kazuyoshi Takeda^{9

10}, Ko Okumura^{9

11}, Masataka Nakamura¹², Tatsukuni Ohno^{9

13}, Yasunari Miyazaki¹

Affiliations

¹ Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
² Department of Respiratory Medicine, Shuuwa General Hospital, Saitama, Japan.
³ Department of Respiratory Medicine, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan.
⁴ Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan.
⁵ Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama, Japan.
⁶ Department of Respiratory Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
⁷ Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
⁸ Allergy Center, National Center for Child Health and Development, Tokyo, Japan.
⁹ Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
¹⁰ Laboratory of Cell Biology, Biomedical Research Core Facilities, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
¹¹ Atopy Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
¹² Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan.
¹³ Oral Health Science Center, Tokyo Dental College, Tokyo, Japan.

PMID: 38599205
DOI: 10.1159/000537840

Abstract

Introduction: Prostaglandin D2 (PGD2), which is produced mainly by Th2 cells and mast cells, promotes a type-2 immune response by activating Th2 cells, mast cells, eosinophils, and group 2 innate lymphoid cells (ILC2s) via its receptor, chemoattractant receptor-homologous molecules on Th2 cells (CRTH2). However, the role of CRTH2 in models of airway inflammation induced by sensitization without adjuvants, in which both IgE and mast cells may play major roles, remain unclear.

Methods: Wild-type (WT) and CRTH2-knockout (KO) mice were sensitized with ovalbumin (OVA) without an adjuvant and then challenged intranasally with OVA. Airway inflammation was assessed based on airway hyperresponsiveness (AHR), lung histology, number of leukocytes, and levels of type-2 cytokines in the bronchoalveolar lavage fluid (BALF).

Results: AHR was significantly reduced after OVA challenge in CRTH2 KO mice compared to WT mice. The number of eosinophils, levels of type-2 cytokines (IL-4, IL-5, and IL-13) in BALF, and IgE concentration in serum were decreased in CRTH2 KO mice compared to WT mice. However, lung histological changes were comparable between WT and CRTH2 KO mice.

Conclusion: CRTH2 is responsible for the development of asthma responses in a mouse model of airway inflammation that features prominent involvement of both IgE and mast cells.

Keywords: Airway hyperresponsiveness; Asthma; CRTH2; ILC2s; Prostaglandin D2.