Fig. 1

Pathophysiology of ITP. Thrombocytopenia in ITP is the result of both increased platelet destruction and suppressed platelet production. Platelet autoantigens are abnormally recognized, processed, and presented by DCs, and then CD4⁺ T helper cells are activated toward a proinflammatory profile, which dictate the differentiation of B cells into autoantibody-secreting plasma cells. Autoantibodies not only mediate platelet phagocytosis by macrophages through Fcγ receptors (FcγRs) but also induce platelet desialylation and subsequent clearance through hepatocyte Ashwell–Morell receptors (AMRs). Splenic macrophages have increased expression of major histocompatibility complex (MHC)-II and CD86 and can also present autoantigens to Th cells. CD8⁺ cytotoxic T lymphocytes (CTLs) can directly lyse platelets or induce platelet apoptosis. Moreover, autoantibodies and CTLs interfere with megakaryocyte maturation and apoptosis, leading to decreased platelet production in ITP. AMR Ashwell–Morell receptor, FcγR Fcγ receptor, M1/M2 M1/M2 macrophage polarization, CDC complement-dependent cytotoxicity, AICD activation-induced cell death, DC dendritic cell, IDO indoleamine 2,3-dioxygenase, Tfh follicular T helper cell, Th T helper cell, Treg regulatory T cell, Breg regulatory B cell, Bmem memory B cell, MHC-II major histocompatibility complex-II, ↓ means decreased or downregulated, ↑ means increased or upregulated