Deficiency of CRTH2, a prostaglandin D 2 receptor, aggravates bleomycin-induced pulmonary inflammation and fibrosis

Soichiro Ueda, Koichi Fukunaga, Takahisa Takihara, Yoshiki Shiraishi, Tsuyoshi Oguma, Tetsuya Shiomi, Yusuke Suzuki, Makoto Ishii, Koichi Sayama, Shizuko Kagawa, Hiroyuki Hirai, Kinya Nagata, Masataka Nakamura, Taku Miyasho, Tomoko Betsuyaku, Koichiro Asano

Research output: Contribution to journalArticle

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Abstract

Chemoattractant receptor homologous with T-helper cell type 2 cells (CRTH2), a receptor for prostaglandin D 2 , is preferentially expressed on T-helper cell type 2 lymphocytes, group 2 innate lymphoid cells, eosinophils, and basophils, and elicits the production of type 2 cytokines, including profibrotic IL-13. We hypothesized that lack of CRTH2 might protect against fibrotic lung disease, and we tested this hypothesis using a bleomycin-induced lung inflammation and fibrosis model in CRTH2-deficient (CRTH2 / ) or wild-type BALB/c mice. Compared with wild-type mice, CRTH2 / mice treated with bleomycin exhibited significantly higher mortality, enhanced accumulation of inflammatory cells 14–21 days after bleomycin injection, reduced pulmonary compliance, and increased levels of collagen and total protein in the lungs. These phenotypes were associated with decreased levels of IFN-g, IL-6, IL-10, and IL-17A in BAL fluid. Adoptive transfer of splenocytes from wild-type, but not CRTH2 / , mice 2 days before injection of bleomycin resolved the sustained inflammation as well as the increased collagen and protein accumulation in the lungs of CRTH2 / mice. We consider that the disease model is driven by gdT cells that express CRTH2; thus, the adoptive transfer of gdT cells could ameliorate bleomycin-induced alveolar inflammation and fibrosis.

Original languageEnglish
Pages (from-to)289-298
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume60
Issue number3
DOIs
Publication statusPublished - 2019 Mar 1

Fingerprint

Prostaglandins D
Pulmonary Fibrosis
Bleomycin
Pneumonia
Th2 Cells
Adoptive Transfer
Fibrosis
Collagen
Formyl Peptide Receptor
Lymphocytes
Inflammation
Lung Compliance
Dimercaprol
Lung
Pulmonary diseases
Injections
Interleukin-13
Basophils
Interleukin-17
Eosinophils

Keywords

  • Bleomycin
  • CRTH2
  • GdT cell
  • IL-10
  • IL-17

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Deficiency of CRTH2, a prostaglandin D 2 receptor, aggravates bleomycin-induced pulmonary inflammation and fibrosis . / Ueda, Soichiro; Fukunaga, Koichi; Takihara, Takahisa; Shiraishi, Yoshiki; Oguma, Tsuyoshi; Shiomi, Tetsuya; Suzuki, Yusuke; Ishii, Makoto; Sayama, Koichi; Kagawa, Shizuko; Hirai, Hiroyuki; Nagata, Kinya; Nakamura, Masataka; Miyasho, Taku; Betsuyaku, Tomoko; Asano, Koichiro.

In: American journal of respiratory cell and molecular biology, Vol. 60, No. 3, 01.03.2019, p. 289-298.

Research output: Contribution to journalArticle

Ueda, S, Fukunaga, K, Takihara, T, Shiraishi, Y, Oguma, T, Shiomi, T, Suzuki, Y, Ishii, M, Sayama, K, Kagawa, S, Hirai, H, Nagata, K, Nakamura, M, Miyasho, T, Betsuyaku, T & Asano, K 2019, ' Deficiency of CRTH2, a prostaglandin D 2 receptor, aggravates bleomycin-induced pulmonary inflammation and fibrosis ', American journal of respiratory cell and molecular biology, vol. 60, no. 3, pp. 289-298. https://doi.org/10.1165/rcmb.2017-0397OC
Ueda, Soichiro ; Fukunaga, Koichi ; Takihara, Takahisa ; Shiraishi, Yoshiki ; Oguma, Tsuyoshi ; Shiomi, Tetsuya ; Suzuki, Yusuke ; Ishii, Makoto ; Sayama, Koichi ; Kagawa, Shizuko ; Hirai, Hiroyuki ; Nagata, Kinya ; Nakamura, Masataka ; Miyasho, Taku ; Betsuyaku, Tomoko ; Asano, Koichiro. / Deficiency of CRTH2, a prostaglandin D 2 receptor, aggravates bleomycin-induced pulmonary inflammation and fibrosis In: American journal of respiratory cell and molecular biology. 2019 ; Vol. 60, No. 3. pp. 289-298.
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AU - Shiraishi, Yoshiki

AU - Oguma, Tsuyoshi

AU - Shiomi, Tetsuya

AU - Suzuki, Yusuke

AU - Ishii, Makoto

AU - Sayama, Koichi

AU - Kagawa, Shizuko

AU - Hirai, Hiroyuki

AU - Nagata, Kinya

AU - Nakamura, Masataka

AU - Miyasho, Taku

AU - Betsuyaku, Tomoko

AU - Asano, Koichiro

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