Inter-Organ Communication in Pulmonary Fibrosis: Systemic Modifiers of a Lung-Centered Disease

Pulmonary fibrosis (PF) is a chronic, progressive interstitial lung disease characterized by recurrent alveolar epithelial injury, aberrant repair, fibroblast activation, excessive extracellular matrix deposition, and irreversible loss of lung function. Although traditionally considered a lung-restricted disorder, increasing evidence suggests that systemic alterations contribute to disease progression and heterogeneity. Complex communication networks between the lung and distant organs, including the gut, liver, thyroid, brain, kidney, cardiovascular system, and oral microbiota, influence fibrosis through immune, metabolic, endocrine, neural, vascular, and microbial pathways. This review systematically summarizes the roles of the gut-lung, liver-lung, thyroid-lung, and brain-lung axes in PF and outlines emerging evidence involving the kidney-lung, cardiopulmonary, and oral-lung microbial axes. This review aims to provide a theoretical basis for a deeper understanding of the systemic pathological mechanisms underlying PF and to offer insights into the development of potential therapeutic targets and novel intervention strategies.