miR-28-5p targeted Rap1b attenuates splenic inflammation infiltration in immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune disease with isolated platelet count decrease. A subset of patients responds inferiorly to the first-line therapies including glucocorticoid and intravenous immunoglobulins (IVIG), of which the underlying mechanisms have not been fully elucidated. We first found that expression of miR-28-5p was obviously increased in complete responders, and decreased to substantially low levels in partial or non-responders. In the passive ITP model, upregulation of miR-28-5p by injecting agomir slightly improved thrombocytopenia, and obviously inhibited the <i>Rap1b</i> gene expression. Luciferase reporter assay demonstrated there was significant decrease of luciferase activity in 293T cells co-transfected with miR-28-5p mimics and plasmids with <i>Rap1b</i> wide-type sequence. Upregulation of miR-28-5p, and downregulation of <i>Rap1b</i> played a favorable role in reducing B cell infiltration in the marginal zone of spleen in mice. However, miR-28-5p exhibited no significant influence on megakaryocyte maturation in ITP both in vitro and in vivo studies. Finally, we confirmed that miR-28-5p upregulation was associated with superior early treatment response in ITP, and possibly functioned by targeting <i>Rap1b</i> gene to inhibit humoral immunity.