sFRP2 promotes airway inflammation and Th17/Treg imbalance in COPD via Wnt/β-catenin pathway

Imbalance between inflammatory Th17 cells and immunosuppressive regulatory T cells (Treg) contributes to the progression of chronic obstructive pulmonary disease (COPD). We aims to investigate roles and mechanisms of secreted frizzled-related protein 2 (sFRP2) in airway inflammation and Th17/Treg differentiation in COPD. sFRP2 was significantly upregulated in the serum of patients with COPD and in human bronchial epithelial (HBE) cells that were exposed to cigarette smoke extract (CSE). sFRP2 was negatively correlated with FEV1/FVC. CSE increased IL-6 and TNF-α in HBE cells, which was reversed by sFRP2 silencing. CSE exposure elevated the percentage of Th17 in CD3⁺ CD8^- cells while reduced the percentage of Treg in CD4⁺CD25⁺ cells. Knockdown of sFRP2 in peripheral blood mononuclear cells (PBMCs) attenuated Th17 differentiation and induced Treg differentiation. CSE suppressed the expression of β-catenin and Cyclin D1 in PBMCs while knockdown of sFRP2 markedly reversed the inhibitory effects of CSE. Wnt/β-catenin inhibition by Dickkopf-1 reversed the inhibitory effect of si-sFRP2 on the production of inflammatory cytokines and imbalance between Th17 and Treg cells caused by CSE. CSE induced sFRP2 potentiated airway inflammation and disturbed Th17/Treg homeostasis by inhibiting β-catenin.