CXCR3-activating peptide inhibits pulmonary fibrosis in a bleomycin mouse model

Abnormal wound healing and dysregulated inflammation in the lung results in scarring and progressive fibrosis, which are hallmarks of Idiopathic Pulmonary Fibrosis (IPF) and post-COVID injury-related lung fibrosis. Chemokine signaling through the CXCR3 receptor and the CXCR3-activating chemokine interferon gamma-inducible protein of 10kD (CXCL10/IP10) have been implicated in the regulation of pulmonary fibrosis with full length CXCL10 preventing pulmonary fibrosis development in preclinical models. Therapeutic use of full length CXCL10p has been limited by protein instability in vivo. To address this challenge, we utilized a CXCL10 activating peptide (CXCL10p) and found that CXCL10p prevents lung fibrosis and inflammation in the bleomycin mouse model. Our findings suggest that CXCL10p may have improved therapeutic potential for the prevention progressive fibrotic lung diseases such as IPF and acute lung injury-related lung fibrosis. NEW & NOTEWORTHY : We show that the intratracheal treatment of CXCL10p in a bleomycin-induced lung injury mouse model of pulmonary fibrosis reduces lung fibrosis and inflammatory cell infiltration. This efficacy is dose- and timing-dependent. This study highlights the improved therapeutic potential of CXCL10p to regulate and reduce pulmonary fibrosis.