graduate student University of Science and Technology of China Hefei City, Anhui, China (People's Republic)
Background: TPO receptor agonist (TPO-RA) is a clinical second-line drug for the treatment of primary thrombocytopenia (ITP). It can promote megakaryocyte maturation and increase platelet production, but its effect on immunosuppressive cells in patients with ITP has not been explored.
Aims: Therefore, in this study, we explore whether TPO-RA can regulate the immune environment of patients with ITP.
Methods: We detected the proportion and functional changes of MDSCs and its downstream T cells in peripheral blood of patients with ITP by flow cytometry, flow cytometry, qPCR and Elisa. Moreover, we analyzed the changes of RNA expression in MDSCs by RNAseq to explore the underlying mechanism.
Results: We found that the proportion and function of myeloid-derived immunosuppressive cells (MDSCs) in ITP patients converted to TPO-RA were significantly higher than those in patients treated with glucocorticoids (GCs). Then we found that the downstream T cells of MDSCs were also affected by immunosuppression: the proportion and function of cytotoxic Th1 cells and CD8+T cells in peripheral blood of patients treated with TPO-RA decreased, while the proportion and function of Treg cells with immunosuppressive function increased. We further proved by MDSCs depletion test that the inhibitory effect of MDSCs in the primordial immune microenvironment of peripheral blood of ITP patients treated with GCs on Th1 cells and the promotion of Treg cells were impaired, while the above MDSCs functions of ITP patients treated with TPO-RA were restored.Finally, through RNA-seq, we found that KLf9 gene was down-regulated in MDSCs cells of patients treated with TPO-RA, thus promoting MDSCs proliferation and immunosuppressive function.
Conclusion(s): These results suggest that TPO-RA can not only promote platelet production, but also play an immunosuppressive role through MDSCs, which provides a new basis for TPO-RA to replace GCs as the first-line treatment of ITP.
