TSLPR-expressing Cell Profiling in Airway and Blood Samples from Severe Asthma Patients

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RATIONALE: Tezepelumab, a thymic stromal lymphopoietin (TSLP)-neutralizing antibody, significantly reduced exacerbations in severe asthma. However, the specific cell types expressing TSLP receptor (TSLPR) in these patients remain largely uncharacterized. This study aimed to comprehensively identify TSLPR expression across various immune and structural cells within airway tissues and peripheral blood of individuals with severe asthma. Methods: Immunofluorescence staining using an anti-TSLPR antibody was performed on bronchoscopic airway mucosal biopsies and induced sputum in severe asthma. Mass cytometry was utilized to comprehensively analyze TSLPR-expressing cells in peripheral blood mononuclear cells (PBMCs) from severe asthma patients. Flow cytometry was employed to compare the proportion of CD4+CCR4+TSLPR+ Th2 cells in PBMCs among non-asthmatic controls, mild/moderate asthmatics, and severe asthmatics. Results: Immunofluorescence staining revealed TSLPR expression in several inflammatory cells in airway tissues, including CD1c+ cDC2, GATA3+ Th2, and IL-17A+ Th17 cells. In induced sputum analysis, infiltrating eosinophils were confirmed to express TSLPR. Mass cytometry analysis of PBMCs demonstrated strong TSLPR expression in activated Th2 cells and lower, yet positive, expression in Th17 cells. Flow cytometry further showed that the proportion of CD4+CCR4+TSLPR+ Th2 cells in severe asthma patients was significantly higher compared to mild/moderate asthma and non-asthma controls. Discussion: These findings highlight TSLPR's involvement in diverse inflammatory pathways in severe asthma and provide insights into the cellular targets of TSLP-neutralizing therapies.

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