Sang Wei, Sun Cai, Zhang Cong, Zhang Dianzheng, Wang Ying, Xu Linyan, Zhang Zhe, Wei Xiangyu, Pan Bin, Yan Dongmei, Zhu Feng, Yan Zhiling, Cao Jiang, Loughran Thomas P, Xu Kailin
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
Department of hematology, Huaibei Miners General Hospital, Anhui Province, China.
Cell Immunol. 2016 Aug-Sep;306-307:35-40. doi: 10.1016/j.cellimm.2016.05.007. Epub 2016 May 30.
Donor-derived CD4(+) T lymphocytes are the major effector cells directly involved in the development of graft-versus-host disease (GVHD). As a negative regulator of immune cell differentiation and development, microRNA-150 (miR-150) induces immunological tolerance in CD4(+) T cells after transplantation. However, the specific mechanisms have not been fully elucidated. In this study, we demonstrated that miR-150 is capable of not only inhibiting proliferation and activation of CD4(+) T cells but also promoting apoptosis. Mechanistically, miR-150 targets v-akt murine thymoma viral oncogene homolog 3 (AKT3), and subsequently downregulates B-cell lymphoma 2 (Bcl-2) interacting mediator of cell death (BIM). We have also demonstrated that re-expression of AKT3 reversed miR-150-mediated inhibition of CD4(+) T lymphocyte development. Therefore, we conclude that miR-150 negatively regulates CD4(+) T cell function by inhibiting the AKT3/BIM signaling pathway. These findings also suggest that manipulating the levels of miRNA-150 could be a valuable strategy in prevention and/or treatment of acute graft-versus-host disease.
供体来源的CD4(+) T淋巴细胞是直接参与移植物抗宿主病（GVHD）发生发展的主要效应细胞。作为免疫细胞分化和发育的负调节因子，微小RNA-150（miR-150）在移植后诱导CD4(+) T细胞产生免疫耐受。然而，其具体机制尚未完全阐明。在本研究中，我们证明miR-150不仅能够抑制CD4(+) T细胞的增殖和活化，还能促进其凋亡。机制上，miR-150靶向v-akt小鼠胸腺瘤病毒癌基因同源物3（AKT3），随后下调细胞死亡的B细胞淋巴瘤2（Bcl-2）相互作用介质（BIM）。我们还证明，AKT3的重新表达逆转了miR-150介导的对CD4(+) T淋巴细胞发育的抑制作用。因此，我们得出结论，miR-150通过抑制AKT3/BIM信号通路对CD4(+) T细胞功能起负调节作用。这些发现还表明，调控miRNA-150的水平可能是预防和/或治疗急性移植物抗宿主病的一种有价值的策略。
