Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, and ultimately fatal diffuse parenchymal lung disease. The molecular mechanisms of fibrosis in IPF patients are not fully understood and there is a lack of effective treatments. For decades, different types of drugs such as immunosuppressants and antioxidants have been tested, usually with unsuccessful results. Although two antifibrotic drugs (Nintedanib and Pirfenidone) are approved and used for the treatment of IPF, side effects are common, and they only slow down disease progression without improving patients’ survival. Macrophages are central to lung homeostasis, wound healing, and injury. Depending on the stimulus in the microenvironment, macrophages may contribute to fibrosis, but also, they may play a role in the amelioration of fibrosis. In this review, we explore the role of macrophages in IPF in relation to the fibrotic processes, epithelial–mesenchymal transition (EMT), and their crosstalk with resident and recruited cells and we emphasized the importance of macrophages in finding new treatments.

Keywords: idiopathic pulmonary fibrosis; activated macrophages; fibrotic macrophages; EMT

Funding: This work was funded by the Cystic Fibrosis Foundation Postdoc-to-Faculty award MARGAR21F5 to C.M. C.H. is supported by a Parker B. Francis Foundation Fellowship and a Doris Duke Charitable Foundation COVID-19 Fund to Retain Clinician Scientists/COVID-19 CARES Retention Program.

Citation: Sari, E.; He, C.; Margaroli, C. Plasticity towards Rigidity: A Macrophage Conundrum in Pulmonary Fibrosis. Int. J. Mol. Sci. 2022, 23, 11443. https://doi.org/10.3390/ijms231911443