Complement protein C1q activates lung fibroblasts and exacerbates silica-induced pulmonary fibrosis in mice.

Pulmonary fibrosis is a progressive fibrotic disease with a poor prognosis and has suboptimal therapeutic options. The complement protein, C1q, which has various functions, such as promoting phagocytosis and signal transduction, has been shown to exacerbate several fibrosis-related diseases such as myofibrosis. In this study, we examined the role and cellular targets of C1q in pulmonary fibrosis. Silica-induced pulmonary fibrotic C1q-deficient mice showed improvement in fibrosis, and intratracheal administration of C1q to normal mice led to the induction of fibrotic changes. Single-cell RNA sequencing analysis revealed the early activation of fibroblasts and type 2 alveolar epithelial cells after intratracheal administration of C1q, and treatment of primary lung fibroblasts with C1q induced the expression of profibrotic genes. Thus, the inhibition of C1q may be regarded as a therapeutic target for pulmonary fibrosis.