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

1 Citation (Scopus)

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

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

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, 60(3), 289-298. https://doi.org/10.1165/rcmb.2017-0397OC