Department of Basic Medicine Science, School of Medicine, Xiamen University, Xiamen, Fujian, People's Republic of China.
State Key Laboratory of Oncogenes and Related Genes, Shang Hai Jiao Tong University, Shanghai, People's Republic of China.
J Leukoc Biol. 2020 Jul;108(1):177-188. doi: 10.1002/JLB.1MA0220-337RR. Epub 2020 Apr 15.
This study tested the hypothesis that PI3K-Akt activity contributes to the superior immune function of IL-15-administrated bone marrow precursor cells (BMPC). Our previous studies revealed that PI3K-Akt play vital role in dendritic cells (DCs) cross-presentation and DC-based CTL priming. Despite the fact that IL-15 serves multiple functions in its therapeutic potential for the induction and maintenance of T cell response, the exact role of PI3K-Akt in IL-15 increased adaptive immunity is still poorly understood. In this study, we demonstrated that ex vivo IL-15 administration increased BMPC capability of antigen uptake and the expression of costimulatory molecules (such as CD80 and 4-1BB(CD137) ligand [4-1BBL]) and MHC class I molecule via PI3K-Akt pathway. Importantly, PI3K-Akt activity was not only necessary for IL-15 augmented BMPC cross-presentation and CTL priming, but also facilitated IL-15 increased therapeutic potential of the cytolytic capacity and maintenance of BMPC-activated T cells. Thus, these data suggested that PI3K-Akt activity contribute to the superior immune function of IL-15-administrated BMPC and thereby might be therapeutic potential for adaptive immunity.
这项研究检验了这样一个假设,即 PI3K-Akt 活性有助于 IL-15 管理的骨髓前体细胞 (BMPC) 的优越免疫功能。我们之前的研究表明,PI3K-Akt 在树突状细胞 (DC) 的交叉呈递和基于 DC 的 CTL 启动中发挥重要作用。尽管 IL-15 在其诱导和维持 T 细胞反应的治疗潜力中具有多种功能,但 PI3K-Akt 在 IL-15 增强适应性免疫中的确切作用仍知之甚少。在这项研究中,我们证明了体外 IL-15 给药通过 PI3K-Akt 途径增加了 BMPC 对抗原的摄取能力以及共刺激分子(如 CD80 和 4-1BB(CD137)配体[4-1BBL])和 MHC 类 I 分子的表达。重要的是,PI3K-Akt 活性不仅是 IL-15 增强的 BMPC 交叉呈递和 CTL 启动所必需的,而且还促进了 IL-15 增加了 BMPC 激活的 T 细胞的细胞溶解能力和维持的治疗潜力。因此,这些数据表明 PI3K-Akt 活性有助于 IL-15 管理的 BMPC 的优越免疫功能,从而可能具有适应性免疫的治疗潜力。