UC Davis

Overall, this review aims to outline IPF regarding macrophage and fibroblast interactions, in addition to the therapeutic roles that macrophages may play in becoming an inhibitory target for IPF. Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory disease in which the tissue surrounding the alveoli within the lungs undergoes fibrosis or permanent scarring. IPF and the consequent disruption to lung blood flow, in addition to the change in immune landscape, will cause severe impact to lung function to the point of fatalities. The estimated number of patients in the United States affected by IPF is between 35,000 and 55,000 cases, with cases expected to rise as older generations continue to grow proportional to the total size of the population.2,53,141,142 Due to a lack of effective therapies, this disease exhibits a median survival time of 3 to 5 years from the time of diagnosis53,140, much worse than many cancer types. In recent years, there has been a renewed appreciation for the role of immune cells in mediating the fibrotic process with an increased interest in the role of macrophages, a type of innate immune cell which responds to environmental stimuli by secreting a wide range of biochemical signaling compounds. Macrophages help to break down the ECM using matrix metalloproteinases (MMPs). Macrophages also produce tissue inhibitors of metalloproteinases (TIMPs) to inhibit the process of ECM breakdown. Macrophages have been shown to be increased in IPF lung tissue and have a significant and poorly appreciated role in mediating fibrosis. In general, fibrotic diseases are characterized by excessive M2-associated and Th2-driven responses. Therefore, macrophages are an attractive target for inhibiting progressive pulmonary fibrosis. Recent literature has further shown that macrophages and fibroblasts directly interact with each other to influence the tissue microenvironment to affect disease outcomes26,28. In other words, both cell types interact to maintain tissue homeostasis. Together, these cells may interact during IPF and the overall fibrotic lung process to affect pulmonary homeostasis and IPF disease progression.