Exosomal miR-146a-5p derived from bone marrow mesenchymal stromal cells regulate Th1/Th2 balance and alleviates immune thrombocytopenia in pregnancy.

Abstract

Immune thrombocytopenia (ITP) is a common hematological disorder. Our previous study has found that exosomal miR-146a-5p derived from bone marrow mesenchymal stromal cells (BMSCs) regulate Th17/Treg balance to alleviate ITP. This work further investigated the role of miR-146a-5p in ITP with pregnancy. Compared with healthy pregnant volunteers, the levels of Th1 cells and IFN-γ were increased, the levels of Th2 cells and IL-4 were decreased in peripheral blood of ITP patients with pregnancy. Then, human BMSCs-exosomes repressed the ratio of Th1/Th2 cells in CD4⁺ T cells, while BMSCs-exosomes with miR-146a-5p inhibitor increased Th1/Th2 cell ratio. Moreover, an ITP mouse model with pregnancy was constructed by administering anti-CD41 antibody in pregnant mice to verify the role of BMSCs-Exo in vivo. BMSCs-Exo elevated the number of platelet and megakaryocyte, improved the function of gastric, spleen and thymus tissues in ITP mice with pregnancy, which attributed to delivery miR-146a-5p. Furthermore, miR-146a-5p interacted with CARD10, and then repressed CARD10/NF-κB signaling pathway. BMSCs-exosomes promoted proliferation and inhibited apoptosis of Dami cells. In conclusion, BMSCs-exosomal miR-146a-5p reduced Th1/Th2 cell ratio to elevate proliferation and inhibit apoptosis of Dami cells, thereby alleviating ITP with pregnancy development. Therefore, miR-146a-5p may be a target for ITP with pregnancy treatment.