The prostaglandin D2 receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge
Open accessAbstract
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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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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Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610 · see citing works
Hirai, H., Tanaka, K., Yoshie, O., Ogawa, K., Kenmotsu, K., Takamori, Y., Ichimasa, M., Sugamura, K., Nakamura, M., Takano, S., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.2.255 · Cited by 1,101 · see citing works
Hata, A. N., & BREYER, R. M. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.06.003 · Cited by 839 · see citing works
Prostaglandin D 2 as a Mediator of Allergic Asthma
Matsuoka, T., Hirata, M., Tanaka, H., Takahashi, Y., Murata, T., Kabashima, K., Sugimoto, Y., Kobayashi, T., Ushikubi, F., Aze, Y., et al. (2000) · Science · doi:10.1126/science.287.5460.2013 · Cited by 743 · see citing works
Spergel, J. M., Mizoguchi, E., Brewer, J. P., Martin, T. R., Bhan, A. K., & Geha, R. S. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1647 · Cited by 638 · see citing works
Self-citationIncreased production of prostaglandin D2 in patients with systemic mastocytosis
Roberts, L. J., Sweetman, B. J., Lewis, R. A., Austen, K. F., & Oates, J. A. (1980) · New England Journal of Medicine · doi:10.1056/nejm198012113032405 · Cited by 423 · see citing works
Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis
Spergel, J. M., Mizoguchi, E., Oettgen, H. C., Bhan, A. K., & Geha, R. S. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5669 · Cited by 383 · see citing works
Self-citationSelective Expression of a Novel Surface Molecule by Human Th2 Cells In Vivo
Nagata, K., Tanaka, K., Ogawa, K., Kemmotsu, K., Imai, T., Yoshie, O., Abé, H., Tada, K., Nakamura, M., Sugamura, K., et al. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.3.1278 · Cited by 377 · see citing works
Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor
Monneret, G., Gravel, S., Diamond, M. P., Rokach, J., & Powell, W. S. (2001) · Blood · doi:10.1182/blood.v98.6.1942 · Cited by 324 · see citing works
Nagata, K., Hirai, H., Tanaka, K., Ogawa, K., Asô, T., Sugamura, K., Nakamura, M., & Takano, S. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01251-x · Cited by 297 · see citing works
Ma, W., Bryce, P. J., Humbles, A. A., Laouini, D., Yalçindağ, A., Alenius, H. T., Friend, D. S., Oettgen, H. C., Gerard, C. J., & Geha, R. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14097 · Cited by 275 · see citing works
Self-citationXue, L., Gyles, S. L., Wettey, F. R., Gazi, L., Townsend, E. R., Hunter, M., & Pettipher, R. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.6531 · Cited by 262 · see citing works
Gervais, F. G., Cruz, R. P., Châteauneuf, A., Gale, S., Sawyer, N., Nantel, F., Metters, K. M., & O’Neill, G. P. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.119919 · Cited by 239 · see citing works
Enhanced Expression of Eotaxin and CCR3 in Atopic Dermatitis
Yawalkar, N., Uguccioni, M., Schärer, J., Braunwalder, J., Karlen, S., Dewald, B., Braathen, L. R., & Baggiolini, M. (1999) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1999.00619.x · Cited by 222 · see citing works
Activation of the Prostaglandin D2 Receptor DP2/CRTH2 Increases Allergic Inflammation in Mouse
Spik, I., Brénuchon, C., Angéli, V., Staumont-Sallé, D., Fleury, S., Capron, M., Trottein, F., & Dombrowicz, D. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3703 · Cited by 213 · see citing works
Satoh, T., 諸井, 里., Aritake, K., Urade, Y., Kanai, Y., Sumi, K., Yokozeki, H., Hirai, H., Nagata, K., Hara, T., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.4.2621 · Cited by 194 · see citing works
Uller, L., Mathiesen, J. M., Alenmyr, L., Korsgren, M., Ulven, T., Högberg, T., Andersson, G. K. A., Persson, C. G. A., & Kostenis, E. (2007) · Respiratory Research · doi:10.1186/1465-9921-8-16 · Cited by 139 · see citing works
Effects of prostaglandin D2 on helper T cell functions
Tanaka, K., Hirai, H., Takano, S., Nakamura, M., & Nagata, K. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.02.151 · Cited by 117 · see citing works
Prostaglandin D2-Induced Eosinophilic Airway Inflammation Is Mediated by CRTH2 Receptor
Shiraishi, Y., Asano, K., Nakajima, T., et al. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.078212 · Cited by 108 · see citing works
Huang, J., Gao, P.-S., Mathias, R. A., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh279 · Cited by 97 · see citing works
Iwasaki, M., Nagata, K., Takano, S., Takahashi, K., Ishii, N., & Ikezawa, Z. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2002.01862.x · Cited by 86 · see citing works
Chevalier, É., Stock, J., Fisher, T., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.4.2056 · Cited by 84 · see citing works
Shiraishi, Y., Asano, K., Niimi, K., Fukunaga, K., Wakaki, M., Kagyo, J., Takihara, T., Ueda, S., Nakajima, T., Oguma, T., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.1.541 · Cited by 78 · see citing works
Xue, L., Barrow, A., & Pettipher, R. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0804090 · Cited by 76 · see citing works
The Role of the Prostaglandin D2 Receptor, DP, in Eosinophil Trafficking
Schratl, P., Royer, J. F., Kostenis, E., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.7.4792 · Cited by 72 · see citing works
Lukacs, N. W., Berlin, A. A., Franz-Bacon, K., Šášik, R., Sprague, L. J., Ly, T. W., Hardiman, G., Boehme, S. A., & Bacon, K. B. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.90351.2008 · Cited by 68 · see citing works
Ruzicka, T., & Auböck, J. (1987) · The Journal of Immunology · doi:10.4049/jimmunol.138.2.539 · Cited by 61 · see citing works
COX-2 inhibition enhances the TH2 immune response to epicutaneous sensitization
Laouini, D., Elkhal, A., Yalçindağ, A., et al. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.03.042 · Cited by 59 · see citing works
Zheng, X., Nakamura, K., Furukawa, H., et al. (2003) · The Journal of Dermatology · doi:10.1111/j.1346-8138.2003.tb00329.x · Cited by 51 · see citing works
Accumulation of CRTH2-positive leukocytes in human allergic nasal mucosa
Shirasaki, H., Kikuchi, M., Kanaizumi, E., et al. (2009) · Annals of Allergy Asthma & Immunology · doi:10.1016/s1081-1206(10)60239-6 · Cited by 37 · see citing works
Increased expression of CRTH2 on eosinophils in allergic skin diseases
Yahara, H., Satoh, T., Miyagishi, C., & Yokozeki, H. (2009) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/j.1468-3083.2009.03267.x · Cited by 36 · see citing works
Hijnen, D., Nijhuis, E. H. J., de Bruin-Weller, M. S., et al. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23932.x · Cited by 35 · see citing works
Boehme, S. A., Chen, E. P., Bacon, K. B., Sasik, R., Sprague, L. J., Ly, T. W., Hardiman, G., & Bacon, K. B. (2008) · International Immunology · doi:10.1093/intimm/dxn118 · Cited by 33 · see citing works
Vinall, S. L., Townsend, E. R., & Pettipher, R. (2007) · Immunology · doi:10.1111/j.1365-2567.2007.02606.x · Cited by 32 · see citing works
Comparison of Eicosanoid Generation by Highly Purified Human Langerhans Cells and Keratinocytes
Rosenbach, T., Czernielewski, J., Hecker, M., et al. (1990) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12874064 · Cited by 29 · see citing works
Boehme, S. A., Franz-Bacon, K., Chen, E. P., et al. (2009) · International Immunology · doi:10.1093/intimm/dxp031 · Cited by 26 · see citing works
Sugimoto, M., Arai, I., Futaki, N., Honma, Y., Sakurai, T., Hashimoto, Y., & Nakaike, S. (2007) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2006.11.007 · Cited by 22 · see citing works
Wang, J., Xu, Y.-C., Zhao, H. W., et al. (2008) · Molecular Biology Reports · doi:10.1007/s11033-008-9349-6 · Cited by 22 · see citing works
Self-citationGenetic variation in CRTh2 influences development of allergic phenotypes
Cameron, L., Depner, M., Kormann, M., et al. (2009) · Allergy · doi:10.1111/j.1398-9995.2009.02053.x · Cited by 21 · see citing works
Activation of the Ras-related GTPase Rap1 by thymocyte TCR engagement and during selection
(2000) · Pure Amsterdam UMC · doi:10.1002/1521-4141(200010)30:10 · Cited by 3 · see citing works
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Kendall, A. C., & Nicolaou, A. (2013) · Progress in Lipid Research · doi:10.1016/j.plipres.2012.10.003 · Cited by 229 · see citing works
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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)
- PMC
- PMC2950231
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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