All- trans retinoic acid protects mesenchymal stem cells from immune thrombocytopenia by regulating the complement-interleukin-1β loop

• Published in: Haematologica (Roma) 2019-08, Vol.104 (8), p.1661-1675
• Main Authors: Zhu, Xiaolu, Wang, Yanan, Jiang, Qian, Jiang, Hao, Lu, Jin, Wang, Yazhe, Kong, Yuan, Chang, Yingjun, Xu, Lanping, Peng, Jun, Hou, Ming, Huang, Xiaojun, Zhang, Xiaohui
• Format: Article
• Language: English
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2018.204446

Enhanced peripheral complement activation has long been considered as one of the major pathogenic elements of immune thrombocytopenia. A dysfunctional bone marrow microenvironment, especially with regards to mesenchymal stem cells, has been observed in patients with immune thrombocytopenia. However, the potential role of the complement system in the dysfunctional bone marrow microenvironment remains poorly understood. In this study, bone marrow samples from patients with immune thrombocytopenia were divided into two groups based on whether or not complement components were deposited on the surfaces of their mesenchymal stem cells. The mesenchymal cells from the group with complement deposition were less numerous, dysfunctional, had a reduced capacity to proliferate, and showed increased apoptosis as well as abnormal secretion of interleukin-1β and C-X-C motif chemokine ligand 12. treatment with all- retinoic acid increased the number and improved the function of the complement-positive bone marrow mesenchymal stem cells by upregulating DNA hypermethylation of the interleukin-1β promoter. studies showed that all- retinoic acid could rescue the impaired mesenchymal stem cells to support the thrombopoietic niche in both patients with immune thrombocytopenia and a murine model of this disease. Taken together, these results indicate that impairment of mesenchymal stem cells, mediated by the complement-interleukin-1β loop, plays a role in the pathogenesis of immune thrombocytopenia. All- retinoic acid represents a promising therapeutic approach in patients with immune thrombocytopenia through its effect of repairing mesenchymal stem cell impairment.