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

Abstract

Background: 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.

Keywords: CD4+CRTh2+ T cells; CRTh2; PGD 2; Th2 cells; biomarker; exacerbation; glucocorticosteroid responsiveness; severe asthma; type 2 immunity.