Fig. 3

Schematic illustration of the pathogenesis of interstitial lung disease in rheumatoid arthritis. Alveolar epithelium injury from cigarette smoking characterized by cellular infiltration and release of pro-fibrotic cytokines including interleukins (IL)-17, IL-13, and transforming growth factor (TGF)-β, chemokines, and growth factors, such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) that promote lung fibroblast proliferation and differentiation to myofibroblasts. Smoking also leads to the generation of citrullinated proteins in lung alveolar cell, which means higher levels of rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPA) can be found in the affected lungs of RA patients in the genetically susceptible individuals. Mechanistic study demonstrated ACPA is pathogenic and induces the release of neutrophil extracellular traps (NETs) which trigger the activation of lung fibroblasts to differentiate into myofibroblast, eventually leading to lung fibrosis formation. In addition, other risk factors including males, elder, and longer duration of RA, can also contribute to the development of RA-ILD. All this eventually leads to the development of lung fibrosis in patients with RA