hUC-MSCs regulating the balance of Th17/Treg in Henoch Schönlein purpura via STAT3 pathway

OBJECTIVE: This study explores the relationship between T helper 17 (Th17)/regulatory T (Treg) cell balance, human umbilical cord mesenchymal stem cells (hUC-MSCs), and immune dysregulation in Henoch-Schönlein purpura (HSP). METHODS: Peripheral blood and clinical data were collected from children with acute HSP and healthy controls. Th17/Treg-related transcription factors and cytokines were measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). In vitro, human umbilical vein endothelial cells were stimulated with HSP serum and co-cultured with hUC-MSCs, with or without the signal transducer and activator of transcription 3 (STAT3) agonist colivelin TFA. STAT3 signaling, interleukin-6 (IL-6) expression, and endothelial migration were analyzed. In vivo, an ovalbumin-induced HSP rat model was treated with hUC-MSCs or stem cells plus colivelin TFA, followed by evaluation of pathological injury, STAT3 activation, and splenic Th17/Treg ratios. RESULTS: Children with HSP exhibited significant Th17/Treg imbalance, with elevated RORγt and IL-17 and decreased FOXP3 and IL-10 (P < 0.05). In vitro, stem cells suppressed IL-6/STAT3 signaling, reduced STAT3 phosphorylation, and promoted endothelial repair, whereas colivelin TFA abolished these effects. In the rat model, stem cell transplantation alleviated inflammation in skin, kidney, joint, and intestinal tissues by downregulating the IL-6/STAT3/RORγt axis and restoring Th17/Treg balance; these benefits were negated by colivelin TFA. CONCLUSION: Th17/Treg imbalance is an immunopathological feature of HSP. hUC-MSCs restore immune homeostasis by inhibiting STAT3 signaling, highlighting STAT3 as a potential therapeutic target and supporting further investigation of stem cell-based therapy.