Obesity-Induced Th17 Inflammation Drives Lung Alterations Without Worsening COPD: Insights into Adipose–Lung Crosstalk.

Background: Obesity and chronic obstructive pulmonary disease (COPD) are major health concerns that share inflammatory pathways. Whether their coexistence exacerbates lung injury remains unclear. Methods: C57BL/6 mice were exposed to cigarette smoke (CS) for months COPD and/or fed a high-fat diet (HFD) obesity. Groups included control, COPD, obesity, obesity + COPD, and obesity + COPD treated with an anti-IL-17 antibody. Lung mechanics, histopathology, inflammatory mediators, and metabolic parameters were assessed. Results: Obesity promoted body mass gain, glucose intolerance, and adipose tissue expansion, while also inducing alveolar enlargement and reduced tissue elastance, changes resembling COPD. Both HFD and CS exposure increased pulmonary IL-17–positive cells and IL-17 levels, with a stronger effect observed in the COPD group. Combined obesity and COPD did not further worsen lung injury compared with either condition alone. Anti-IL-17 therapy attenuated lung inflammation, structural destruction, and metabolic dysfunction. Conclusions: Obesity alone triggers Th17/IL-17–mediated lung alterations similar to those observed in COPD, but their coexistence does not synergistically worsen disease features. These findings highlight IL-17 as a pivotal mediator linking adipose tissue inflammation and pulmonary injury and support the concept of adipose–lung crosstalk. Targeting the Th17/IL-17 axis may represent a therapeutic strategy for obesity-associated pulmonary complications.