circDCBLD2 regulates the Th1/Th2 immune balance via the miR-26a-5p/PTEN axis

Asthma is a prevalent chronic respiratory disease in children. Recently, adjusting the Th1/Th2 imbalance has become a significant focus in asthma immunotherapy. The present study aims to investigate the roles and mechanisms of circDCBLD2 in maintaining the Th1/Th2 immune balance. CircDCBLD2 is downregulated in CD4 ⁺ T cells from asthmatic patients and in CD4 ⁺ T cells from an OVA-induced asthmatic mouse model. Additionally, circDCBLD2 levels are significantly decreased in the PBMCs of asthmatic mice. The expression of circDCBLD2 is positively correlated with the Th1 cytokines IFN-γ and IL-2 but negatively correlated with the Th2 cytokines IL-4 and IL-13. Flow cytometry and ELISA analyses demonstrate that circDCBLD2 overexpression increases the proportion of Th1 cells (CD4 ⁺ IFN-γ ⁺) and the levels of Th1 cytokines while decreasing the proportion of Th2 cells (CD4 ⁺ IL-4 ⁺) and the levels of Th2 cytokines. Furthermore, circDCBLD2 overexpression alleviates the asthma phenotype in OVA-induced mice, reduces the infiltration of inflammatory cells in the lungs, and corrects the Th1/Th2 imbalance. Mechanistically, circDCBLD2 is found to target miR-26a-5p. Rescue experiments indicate that circDCBLD2 regulates the Th1/Th2 immune balance by targeting miR-26a-5p. Additionally, PTEN has been identified as a direct target of miR-26a-5p. The overexpression of PTEN partially reverses the effects of miR-26a-5p on the Th1/Th2 immune balance. These findings indicate that circDCBLD2 increases the proportion of Th1 cells and decreases the proportion of Th2 cells via the miR-26a-5p/PTEN axis, providing a promising target for asthma treatment.