Modulation of Specific Breg, Treg, and Th17 Cell Subsets by Yiqi Huatan Huoxue Tang in Juvenile Experimental Autoimmune Thyroiditis Mice

Autoimmune thyroiditis (AIT) is increasingly prevalent in children and frequently associated with cognitive decline. The traditional Chinese formula Yiqi Huatan Huoxue Tang (YQHT) has shown clinical efficacy, yet its mechanistic role in juvenile AIT remains unexplored.To elucidate the multi-target immunomodulatory effects of YQHT and its active component quercetin on the Breg–Treg/Th17 axis in a juvenile AIT mouse model with comorbid cognitive impairment.Network pharmacology and molecular docking analyses identified the IL-17 signaling pathway as the core pathway, with quercetin as a key ligand. A juvenile female BALB/c mouse model (14 days old) of AIT was established and treated with low/medium/high-dose YQHT (12.1, 24.2, 48.4 g·kg⁻¹·d⁻¹) or quercetin (50 mg·kg⁻¹·d⁻¹) for 8 weeks. Cognitive function was assessed using the Morris water maze. Evaluations included thyroid and brain histopathology, serum TGAb/TPOAb levels, splenic proportions of Breg (CD19⁺CD1d⁺CD5⁺IL-10⁺, etc.), Treg, and Th17 cells, as well as mRNA expression of related cytokines.The results showed thatMed-dose YQHT and quercetin alleviated cognitive deficits and thyroid pathology in AIT mice, reduced TPOAb levels, restored Breg frequency, and suppressed Th17 differentiation along with IL-17/TNF-α expression. In vitro experiments further confirmed that YQHT-treated B cells dose-dependently inhibited Th17 polarization.In conclusion, YQHT and quercetin restore Breg/Treg–Th17 balance by inhibiting the IL-17 pathway, providing a mechanistic basis for the treatment of AIT in children.