Deficiency of CRTH2, a Prostaglandin D2 Receptor, Aggravates Bleomycin-Induced Pulmonary Inflammation and Fibrosis.

Chemoattractant receptor homologous with Th2 cells (CRTH2), a receptor for prostaglandin D2 is preferentially expressed on Th2 lymphocytes, group 2 innate lymphoid cells, eosinophils, and basophils, and elicits production of type2 cytokines including profibrotic IL-13. We supposed lack of CRTH2 might be protective role against fibrotic lung disease and examined bleomycin-induced lung inflammation and fibrosis model with CRTH2-deficient (CRTH2-/-) or wild-type BALB/c mice. Compared to the wild-type, 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-γ, IL-6, IL-10, and IL-17A in bronchoalveolar lavage fluid. Adoptive transfer of splenocytes from wild-type, but not from CRTH2-/- mice, 2 days prior to 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 γδT cells that express CRTH2: thus, the adoptive transfer of γδT cells could ameliorate bleomycin-induced alveolar inflammation and fibrosis.