PTX3 regulates immune infiltration and epithelial/fibroblast repair and regeneration in idiopathic pulmonary fibrosis

Several studies have shown a potential protective role of long pentraxin 3 (PTX3) in different lung pathologies. In the present study, we have explored the influence of PTX3 in the bleomycin (BLM)-induced murine model of Idiopathic Pulmonary Fibrosis (IPF). We made a picture of the pulmonary microenvironment by looking at inflammatory infiltrate (macrophages, mast cells, T cells) and stemness/regenerative markers of lung epithelium (SOX2) and fibroblasts/myofibroblasts (CD44) at different time points that retrace the progression of the disease from onset at day 14, to full-blown disease at day 21, to incomplete regression at day 28. We took advantage of transgenic PTX3 overexpressing mice (Tie2-PTX3) and Ptx3 null ones (PTX3-KO) in which IPF was indued. Our data have shown that: throughout the whole experimental period, the CD68+ and CD163+ macrophages and the Tryptase+ mast cells are reduced in the Tie2-PTX3 pulmonary microenvironment compared to wild-type (WT) or PTX3-KO; on the contrary, CD4+ T cells are consistently present on day 14 and dramatically decreased on day 21 in Tie2-PTX3 compared to WT or PTX3-KO; CD8+ T cells do not show significant differences on day 14, but are significantly reduced on day 21 in Tie2-PTX3 compared to WT or PTX3-KO; SOX2 is reduced on days 14 and 21 in Tie2-PTX3 compared to WT or PTX3-KO; CD44 is reduced on day 21 in Tie2-PTX3 compared to WT or PTX3-KO. This scenario demonstrates the anti-inflammatory effects of PTX3, which reduces pro-inflammatory cells and counteracts profibrotic events.