The Immunoregulatory Role of Integrins in Pulmonary Diseases

Qing Xu¹Chao Yang²Wanwen Li³Weiwei Qian⁴Shiyin Chen^5*Liqing Yang^5*

• ¹Respiratory and Critical Care Medicine, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
• ²Medicine Surgery， Sichuan Provincial People's Hospital, School of Medicine,University of Electronic Science and Technology of China, Chengdu, China
• ³Department of Thoracic Surgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
• ⁴Emergency Department, Chengdu Shangjin Nanfu Hospital, Chengdu, China
• ⁵Department of Chinese medicine, Sichuan Provincial People's Hospital, School of Medicine,University of Electronic Science and Technology of China, Chengdu, China

Integrins are a family of transmembrane adhesion receptors composed of α and β subunits that connect cells to the extracellular matrix and transmit biochemical and mechanical signals. They play a critical role in immune cell migration, maintenance of the alveolar-capillary barrier, and tissue repair. Pulmonary diseases often exhibit pathological features of immune imbalance, barrier disruption, and abnormal remodeling. Integrins, situated at the intersection of "cell-matrix-mechanical" signaling, exert decisive influence on disease progression by regulating mechanisms such as neutrophil and monocyte transendothelial migration, TGF-β activation, and the immune microenvironment. This review comprehensively summarizes the structural basis and bidirectional signaling mechanisms of integrins, along with their regulatory roles in the functions of pulmonary immune cells such as T cells, macrophages, and neutrophils. It emphasizes the pathological mechanisms of integrins in diseases including ARDS, pulmonary fibrosis, COPD, asthma, and lung cancer (particularly the dual role of the integrin-TGF-β axis in inflammation and fibrosis) It introduces current and emerging targeted therapeutic strategies, including αvβ6 monoclonal antibodies, small-molecule antagonists, inhaled delivery, and biomimetic delivery approaches. We emphasize that balancing the suppression of pathogenic signals with the maintenance of tissue homeostasis is essential when targeting integrins for therapeutic intervention. Future progress will depend on This is a provisional file, not the final typeset article developing more precise delivery technologies and patient stratification strategies to advance the translational application of integrin-targeted therapies across multiple pulmonary diseases.