Airway epithelial TSLP production is increased in COPD patients

Background: Thymic Stromal Lymphopoietin (TSLP) is a pro-inflammatory cytokine acting as an alarmin in the airways. Recent evidence indicates that TSLP is dysregulated in chronic inflammatory diseases. Objectives: Since COPD pathogenesis is characterized by airway remodeling and inflammation, we investigated the production and localization of TSLP and its receptor CRL2 in the pulmonary cell populations in bronchi and bronchioles of COPD and non-COPD patients. Methods: Gene expression was investigated using single-cell RNAseq analysis, and RTqPCR on airway epithelial cells from bronchial brushings of COPD and non-COPD patients (n=20). Immunostainings on bronchial and bronchiolar formalin-fixed paraffin-embedded sections (n=18) were performed to analyze TSLP and CRL2 production and localization in COPD and non-COPD epithelia. Results: TSLP transcripts were detected in 12% of basal cells in non-COPD patients. There was an increase of 18% in transcript levels in COPD airway epithelial cells (p<0.05 vs non-COPD). The localization of TSLP did not differ in the bronchi of COPD patients (vs non-COPD patients). Bronchiolar TSLP was increased by 70% (p<0.05) in mild COPD patients (vs non-COPD), especially in former smokers (91%, p<0.01 vs active smokers). CRL2 detection was decreased by 31% in COPD bronchi of active smokers (p<0.05 vs non-COPD). No difference was noted in bronchiolar epithelia regarding CRL2. Conclusions: These results highlight the differential expression and localization of TSLP in the small airways and CRL2 in the large airways of COPD patients. Correlating the levels of TSLP production with the immune response in COPD patients may identify a population that could benefit from anti-alarmin therapeutic approaches.