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

BackgroundChemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) is a receptor for PGD(2) 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 PGD(2)-CRTh2 pathway in the lungs was associated with severe asthma. ObjectiveTo assess circulating levels of Th2 cells and related mediators in severe asthma and those who experience asthma exacerbations. MethodsPeripheral blood cells expressing CRTh2 were characterized by flow cytometry and qRT-PCR. Serum IL-13 and PGD(2) were measured by ELISA and compared with asthma severity and tendency to exacerbate. ResultsSevere 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 RelevanceElevated 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.