Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA.
Int J Mol Sci. 2020 Aug 31;21(17):6295. doi: 10.3390/ijms21176295.
CD4 T cells are one of the key immune cells contributing to the immunopathogenesis of type 1 diabetes (T1D). Previous studies have reported that platelet-derived mitochondria suppress the proliferation of peripheral blood mononuclear cells (PBMC). To further characterize the immune modulation of platelet-derived mitochondria, the purified CD4 T cells were treated, respectively, with platelet-derived mitochondria. The data demonstrated that MitoTracker Deep Red-labeled platelet-derived mitochondria could directly target CD4 T cells through C-X-C motif chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1 (SDF-1), regulating the anti-CD3/CD28 bead-activated CD4 T cells. The result was an up-regulation of Naïve and central memory (T) CD4 T cells, the down-regulation of effector memory (T) CD4 T cells, and modulations of cytokine productions and gene expressions. Thus, platelet-derived mitochondria have a translational potential as novel immune modulators to treat T1D and other autoimmune diseases.
CD4 T 细胞是导致 1 型糖尿病(T1D)免疫发病机制的关键免疫细胞之一。先前的研究报告指出,血小板衍生的线粒体可抑制外周血单个核细胞(PBMC)的增殖。为了进一步研究血小板衍生的线粒体的免疫调节作用,分别用血小板衍生的线粒体处理纯化的 CD4 T 细胞。数据表明,MitoTracker Deep Red 标记的血小板衍生线粒体可通过 C-X-C 基序趋化因子受体 4(CXCR4)及其配体基质细胞衍生因子 1(SDF-1)直接靶向 CD4 T 细胞,调节抗 CD3/CD28 珠激活的 CD4 T 细胞。结果表现为幼稚和中央记忆(T)CD4 T 细胞上调,效应记忆(T)CD4 T 细胞下调,细胞因子产生和基因表达的调节。因此,血小板衍生的线粒体具有作为治疗 T1D 和其他自身免疫性疾病的新型免疫调节剂的转化潜力。