Taming the immune storm: The pivotal role of tolerogenic dendritic cells in the pathogenesis and treatment of immune thrombocytopenia.

Dendritic cells (DCs) serve as pivotal modulators of immune reactions, linking innate and adaptive immunity through their antigen-presenting capability. Among DC subsets, tolerogenic DCs (tolDCs) are uniquely equipped to foster immune tolerance by suppressing effector T-cell activation and facilitating the induction of regulatory T cells (Tregs). In immune thrombocytopenia (ITP), tolDCs have demonstrated therapeutic promise by employing mechanisms such as cytokine-driven suppression and restructuring of the bone marrow (BM) microenvironment via interactions with mesenchymal stem cells. Key findings demonstrate that tolDCs can reduce anti-platelet autoantibodies and stabilize platelet counts in preclinical ITP models. Emerging strategies, including autologous reinfusion, genetic modifications to enhance stability, and combinations with thrombopoietin receptor agonists or glucocorticoids, provide promise for sustained remission. However, challenges remain, including phenotypic instability and production scalability. This review synthesizes these insights, emphasizing the potential of tolDCs to advance ITP-specific immunotherapies beyond conventional treatments. Additionally, this review outlines the sources of tolDCs and their regulatory mechanisms, examines their relevance in autoimmune conditions, and provides new perspectives on ITP pathogenesis and therapy.