Abstract
Lung fibrosis is developed in severe asthmatic patients, whereas the mechanisms are unclear. We have established a murine model of steroid-insensitive asthma, which shows lung fibrosis. RNA-seq analyses revealed genes encoding CCR5 and its ligands were upregulated in the lung. However, roles of CCR5 in the development of fibrosis were unclear. In this study, we analyzed whether a CCR5 antagonist, maraviroc improves the fibrosis and increase in one of profibrotic cell types, monocyte-derived alveolar macrophages (MoAMs). OVA-sensitized BALB/c mice were intratracheally challenged with OVA. Dexamethasone (DEX, 1 mg/kg i.p.) or maraviroc (50 mg/kg p.o.) was administered during the challenges. The development of lung fibrosis and the number of MoAMs (CD45+ CD64+ Ly-6C+ Ly-6G-/low Siglec-F-) in the lung were analyzed. Maraviroc improved the development of lung fibrosis, whereas DEX did not affect it. Increase in MoAMs was suppressed by neither DEX nor maraviroc. Yet, interestingly, the number of CCR5+ cells were decreased in the maraviroc-treated mice. The decreased CCR5+ cells expressed CD45, CD11b, Ly-6C and Ly-6G, which displayed phenotype of monocyte-derived suppressor cells (MDSC). It was suggested that CCR5 possibly contributes to the increase in CCR5+ MDSC-like profibrotic cells, leading to the development of lung fibrosis.
