Su Ning, Shi Samuel X, Zhu Xiaodong, Borazanci Aimee, Shi Fu-Dong, Gan Yan
Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, United States; Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, United States.
J Neuroimmunol. 2014 Nov 15;276(1-2):180-6. doi: 10.1016/j.jneuroim.2014.08.618. Epub 2014 Aug 27.
Decreased NK cell numbers and impairment of NK cell function are reported in patients with multiple sclerosis (MS). Interleukin-7 (IL-7) is a member of the common gamma-chain (γc) cytokine superfamily that has well documented roles in lymphocyte development and homeostasis. The interleukin-7 receptor α chain (IL-7Rα) gene was identified as a top non-major histocompatibility complex-linked risk locus for MS. The objective of this study was to test biological function of IL-7/IL-7Rα on NK cells in MS patients. We observed markedly lower IL-7 levels in MS sera, and relatively higher IL-7Rα expression in NK cells of MS. Upon IL-7 stimulation, IL-7Rα on NK cells from MS patients was significantly down-regulated compared with healthy controls (HCs). IL-7 induced a higher increase of IFN-γ production in CD56(bright) NK cells and a pronounced enhancement of cytotoxicity in NK cells from MS. IL-7 did not impact the proliferation of NK cells differently in MS and HC. In contrast, IL-7 promoted a higher survival of CD56(bright) NK cells in MS and inhibited their apoptosis by increasing Bcl-2 expression, but had no effect on CD56(dim) NK cell survival in MS. In conclusion, MS patients have lower serum IL-7 and a higher membrane IL-7Rα expression on CD56(bright) NK cells. The skew at the IL-7 and IL-7Rα level influences functional responsiveness of NK cells in MS.
据报道，多发性硬化症（MS）患者的自然杀伤（NK）细胞数量减少且功能受损。白细胞介素-7（IL-7）是常见γ链（γc）细胞因子超家族的成员，在淋巴细胞发育和内环境稳定中具有充分记录的作用。白细胞介素-7受体α链（IL-7Rα）基因被确定为MS的一个主要非主要组织相容性复合体连锁风险位点。本研究的目的是测试IL-7/IL-7Rα对MS患者NK细胞的生物学功能。我们观察到MS患者血清中IL-7水平明显较低，而MS患者NK细胞中IL-7Rα表达相对较高。经IL-7刺激后，与健康对照（HCs）相比，MS患者NK细胞上的IL-7Rα明显下调。IL-7诱导MS患者CD56（明亮）NK细胞中IFN-γ产生的增加更高，且MS患者NK细胞的细胞毒性明显增强。IL-7对MS和HC中NK细胞增殖的影响无差异。相反，IL-7促进了MS患者CD56（明亮）NK细胞的更高存活，并通过增加Bcl-2表达抑制其凋亡，但对MS患者CD56（暗淡）NK细胞的存活没有影响。总之，MS患者血清IL-7水平较低，CD56（明亮）NK细胞上膜IL-7Rα表达较高。IL-7和IL-7Rα水平的偏差影响了MS患者NK细胞的功能反应性。
