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

Area of Science:

• Immunology
• Respiratory Medicine
• Allergy and Clinical Immunology

Background:

• Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) is a PGD2 receptor found on T cells, eosinophils, basophils, and ILC2 cells.
• CRTh2 expression on CD4(+) T cells defines the Th2 subset, linked to allergen-specific central memory Th2 cells.
• The PGD2-CRTh2 pathway activation in the lungs is recently associated with severe asthma.

Purpose of the Study:

• To evaluate circulating Th2 cell levels and associated mediators in severe asthma patients.
• To identify correlations between Th2 cell levels, asthma severity, and exacerbation frequency.

Main Methods:

• Peripheral blood CD4(+) CRTh2(+) T cells were analyzed using flow cytometry and qRT-PCR.
• Serum levels of Interleukin-13 (IL-13) and Prostaglandin D2 (PGD2) were quantified via ELISA.
• These mediators were compared against asthma severity and exacerbation history.

Main Results:

• Severe asthmatics exhibited higher circulating CD4(+) CRTh2(+) T cells, CRTh2, GATA3 mRNA, and serum IL-13 compared to mild/moderate cases.
• The proportion of CD4(+) CRTh2(+) T cells correlated with reduced lung function and was highest in severe asthmatics with recent exacerbations.
• Unlike eosinophils, circulating CD4(+) CRTh2(+) T cells showed a positive correlation with inhaled corticosteroid dosage.

Conclusions:

• Increased circulating CD4(+) CRTh2(+) T cells are characteristic of severe asthma, persisting despite high-dose corticosteroid therapy.
• Monitoring systemic CD4(+) CRTh2(+) T cell levels could aid in identifying Type 2 severe asthmatics prone to exacerbations.