Exosomal MiR-146a-5p Derived from Bone Marrow Mesenchymal Stromal Cells Regulate Th1/Th2 Balance and Alleviates Immune Thrombocytopenia in Pregnancy

Overview

Journal Hum Cell

Publisher Springer

Specialty Cell Biology

Date 2024 Dec 19

PMID 39699695

Authors

Yanyan Rong

Wei Lu

Xianbao Huang

Dexiang Ji

Dehong Tang

Ruibin Huang

Wenhua Zhou

Guoan Chen

Yue He

Affiliations

Soon will be listed here.

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.

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PMID: 39692857 DOI: 10.1007/s00204-024-03920-1.

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