The immunopathophysiology of organ fibrosis: From mechanisms to immunotherapies

Fibrosis is the ultimate outcome of various chronic diseases that affect multiple organs, including the liver, lungs, heart, and kidneys. This pathological process is characterized by the excessive accumulation of extracellular matrix produced by activated myofibroblasts in response to chronic injury, as part of a degenerative process of dysregulated tissue repair. Although numerous pathways have been implicated in the development of fibrosis, the precise mechanisms that drive and exacerbate organ fibrosis remain inconclusive. Consequently, there are currently very limited treatments for organ fibrosis. In recent years, immune cells have been identified as critical mediators of the fibrotic cascade, capable of inducing tissue damage or promoting repair. Harnessing immune cells and immunotherapeutic approaches to intervene in the fibrotic process is a promising avenue toward new treatment options. In this review, we explore the pathophysiology of fibrosis in various organs, with a specific focus on the role of immune cells in both the development and regression of fibrosis as well as the latest preclinical findings in relation to immunotherapeutic treatment approaches. Understanding the role of immune responses in fibrotic diseases will aid in the development of immunotherapeutic strategies that target key profibrotic cytokines and immune cells, with the aim of preventing fibrosis or promoting its regression.