| First Author | Ueda S | Year | 2019 |
| Journal | Am J Respir Cell Mol Biol | Volume | 60 |
| Issue | 3 | Pages | 289-298 |
| PubMed ID | 30326727 | Mgi Jnum | J:288889 |
| Mgi Id | MGI:6416603 | Doi | 10.1165/rcmb.2017-0397OC |
| Citation | Ueda S, et al. (2019) Deficiency of CRTH2, a Prostaglandin D2 Receptor, Aggravates Bleomycin-induced Pulmonary Inflammation and Fibrosis. Am J Respir Cell Mol Biol 60(3):289-298 |
| abstractText | Chemoattractant receptor homologous with T-helper cell type 2 cells (CRTH2), a receptor for prostaglandin D2, 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-gamma, 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 gammadeltaT cells that express CRTH2; thus, the adoptive transfer of gammadeltaT cells could ameliorate bleomycin-induced alveolar inflammation and fibrosis. |
