Elevated levels of circulating CD4+CRTh2+ T cells characterize severe asthma

SummaryBackground Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) is a receptor for PGD2 and expressed by T cells, eosinophils, basophils, and ILC2 cells. CRTh2 expression by CD4+ T cells identifies the Th2 subset, and these cells have been characterized as allergen-specific central memory Th2 cells. Recently, activation of the PGD2-CRTh2 pathway in the lungs was associated with severe asthma. Objective To assess circulating levels of Th2 cells and related mediators in severe asthma and those who experience asthma exacerbations. Methods Peripheral blood cells expressing CRTh2 were characterized by flow cytometry and qRT-PCR. Serum IL-13 and PGD2 were measured by ELISA and compared with asthma severity and tendency to exacerbate. Results Severe asthmatics had more circulating CD4+CRTh2+ T cells, CRTh2 and GATA3 mRNA, and a higher level of serum IL-13 compared to mild/moderate asthmatics. The proportion of CD4+CRTh2+ T cells was associated with lower lung function and was highest in severe asthmatics that exacerbated in the last year. Circulating CD4+CRTh2+ T cells, unlike eosinophils, were positively correlated with inhaled steroid dose. Conclusions and Clinical Relevance Elevated levels of circulating CD4+CRTh2+ T cells are a feature of severe asthma, despite high-dose corticosteroids. Tracking the systemic level of these cells may help identify type 2 severe asthmatics at risk of exacerbation.