Echinococcus granulosus antigen B regulates T-cell function through inhibition of signal transducer and activator of transcription 3 in experimental immune thrombocytopenia.

Dysregulated T-cell homeostasis is central to the development of immune thrombocytopenia (ITP), characterized by reduced platelet counts. Antigen B (AgB), a key protein in Echinococcus granulosus cyst fluid, modulates T-cell differentiation and reduces inflammation. Here, we explored the role of AgB in ITP and found that it enhances the generation and function of regulatory T cells (Tregs), boosting their immunosuppressive activity. In our passive ITP murine model, AgB treatment alleviated thrombocytopenia and restored the Treg-helper T-cell (Th) balance. However, the therapeutic effects of AgB on CD4+ T cells were abolished by Treg depletion, highlighting the essential role of Tregs in AgB's mechanism of action. Moreover, AgB reduced proinflammatory cytokine production and inhibited signal transducer and activator of transcription 3 (STAT3) activation in ITP mice, with STAT3 inhibition negating the effects of AgB in Tregs. AgB promoted STAT3 degradation via tumour necrosis factor receptor-associated factor 6 (TRAF6)-mediated ubiquitination. In conclusion, by facilitating TRAF6-mediated STAT3 ubiquitination, AgB restores T-cell homeostasis and strengthens Treg immunosuppression, affording a potential therapeutic strategy for ITP.