Dysregulated negative immune regulators in immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune disease mediated by IgG antiplatelet autoantibodies, resulting in an isolated thrombocytopenia. The mechanism for ongoing antiplatelet antibody production is explained by a ‘pathogenic loop’ model consisting of macrophages in the reticuloendothelial system, platelet-reactive CD4+ T cells and B cells producing IgG antiplatelet antibodies. In ITP patients, a variety of negative immune regulators including CD4+ T regulatory cells, B regulatory cells and tolerogenic dendritic cells are dysfunctional, resulting in failure to efficiently suppress the pathogenic loop. In addition, Helicobacter pylori infection leads to defective inhibitory FcγRIIB signalling in macrophages and thereby increases susceptibility to ITP. In ITP patients, dysregulation of these negative immune regulators is associated with each other in the impaired immune regulatory network. Thus, strategies that enhance functions of these intrinsic negative immune regulators would be promising future approaches for treating ITP.