Cited by 54Dermatology and Skin DiseasesAsthma and respiratory diseasesContact Dermatitis and Allergies

The prostaglandin D2 receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge

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He, Rui, Oyoshi, Michiko K., Wang, James Y.T., Hodge, Martin R., Jin, Haoli, Geha, Raif S.·2010·Journal of Allergy and Clinical Immunology

Abstract

Background Cutaneous prostaglandin (PG) D₂ levels increase after scratching. Chemoattractant receptor-homologous molecule expressed on receptor on T(H)2 cells (CRTH2) mediates chemotaxis to PGD₂ and is expressed on T(H)2 cells and eosinophils, which infiltrate skin lesions in patients with atopic dermatitis.Objective We sought to examine the role of CRTH2 in a murine model of atopic dermatitis.Methods CRTH2(-/-) mice and wild-type control animals were epicutaneously sensitized by means of repeated application of ovalbumin (OVA) to tape-stripped skin for 7 weeks and then challenged by means of OVA application to tape-stripped previously unsensitized skin for 1 week. Skin histology was assessed by means of hematoxylin and eosin staining and immunohistochemistry. Cytokine mRNA expression was examined by means of quantitative RT-PCR. Levels of PGD₂, antibody, and cytokines were measured by means of ELISA.Results PGD₂ levels significantly increased in skin 24 hours after tape stripping, although not in skin subjected to repeated sensitization with OVA. Allergic skin inflammation developed normally at sites of chronic epicutaneous sensitization with OVA in CRTH2(-/-) mice but was severely impaired in previously unsensitized skin challenged with OVA, as evidenced by significantly decreased skin infiltration with eosinophils and CD4(+) cells and impaired T(H)2 cytokine mRNA expression. Impaired skin inflammation at sites of acute OVA challenge in CRTH2(-/-) mice was not due to an impaired systemic response to epicutaneous sensitization because OVA-specific IgG1 and IgE antibody levels and OVA-driven splenocyte secretion of cytokines in these mice were comparable with those seen in wild-type control animals.Conclusions CRTH2 promotes allergic skin inflammation in response to cutaneous exposure to antigen in previously sensitized mice.

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Crossref · 10.1016/j.jaci.2010.07.006

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  • In vitro and animal-model evidence indicates that CRTH2 has an important role in TH2-mediated AD inflammation by directing migration into the skin.

    “as shown in vitro and in animal models154,155, has an important role in TH2-mediated inflammation of AD by directing their migration into the skin.”

    From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [155]

    The Introduction reports CRTH2-mediated chemotaxis in vitro, and the Results section on acute OVA challenge reports reduced skin infiltration by CD4+ cells and eosinophils in CRTH2-deficient mice (page numbers unavailable). But the Results on repeated sensitization find no important role for CRTH2 in chronic skin inflammation. The evidence therefore supports migration-related inflammation in an acute mouse model, not an unqualified role in AD inflammation. (LLM, conf=0.86)

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Authors
He, R., Oyoshi, M. K., Wang, J. Y. T., Hodge, M. R., Jin, H., & Geha, R. S.
Affiliations
  • Boston Children's Hospital (US)
  • Biogen (United States) (US)
Corresponding author
Geha, Raif S.
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2010-10
Volume
126
Issue
4
Pages
784-790
ISSN
0091-6749 (ISSN-L)
OpenAlex
W2029473902
Cited by
54
References
40
Citations by year
2025: 3 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 5 · 2018: 8 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 7
FWCI
6.95
Type
journal article
Language
en
Open access
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (n01ai40030-7-0-0)
  • National Institute of Allergy and Infectious Diseases (N01 AI040030, AI 40030, N01 AI400030)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR047417, AR-047417)
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
Keywords
CRTH2, prostaglandin D2, allergic skin inflammation, atopic dermatitis, epicutaneous sensitization, ovalbumin, eosinophils, Th2 cells, IgE, cytokine expression
MeSH terms
Administration, Cutaneous, Animals, Chemotaxis, Leukocyte, Dermatitis, Atopic, Female, Humans, Mice, Inbred BALB C, Ovalbumin, Receptors, Immunologic, Receptors, Prostaglandin, Skin, Prostaglandin D2, Mice, Knockout, Th2 Cells, Mice

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