Suppressed autophagy of thymic cells promotes apoptosis and thymic atrophy in COPD.

Abstract

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent and incurable condition characterized by persistent inflammation and systemic complications. Although the thymus is traditionally believed to undergo involution in adulthood, it continues to play a critical role in immune regulation and tumor surveillance. However, its specific involvement in COPD remains largely unexplored. OBJECTIVES: This study aimed to investigate the presence and mechanisms of thymic atrophy in COPD. METHODS: Thymic atrophy was assessed in COPD patients through chest CT imaging and further validated in a cigarette smoke-induced COPD mouse model. We examined thymic cell counts, levels of apoptosis, epithelial-mesenchymal transition (EMT) markers, expression of aging-related markers (p53 and p21), and autophagy activity with related pathway signals. RESULTS: Chest CT scans from 251 subjects revealed progressive thymic atrophy in COPD patients, correlating with disease severity. In COPD model mice, histological analysis showed reduced thymocyte counts, increased apoptosis, and selective loss of CD8⁺ T cells. EMT features were observed, along with decreased autophagy markers and disrupted PI3K/mTOR signaling. CONCLUSION: COPD is associated with severe thymic atrophy potentially driven by impaired autophagy and aging-related apoptosis, offering new insights into immune dysfunction and potential therapeutic targets.