Department of Immunology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130021, China.
Department of Anatomy, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Biol Chem. 2020 Feb 25;401(2):297-308. doi: 10.1515/hsz-2019-0245.
Interleukin-9 (IL-9) is a cytokine secreted by T-helper (Th)9 cells, and activin A can enhance Th9 cell differentiation. However, whether activin A affects IL-9 production by natural killer (NK) cells remains unclear. Herein, we found that not only Th cells, but also CD3-CD49b+NKp46+ NK cells of Balb/c mice produced IL-9. Although activin A promoted IL-9 expression in CD4+ Th cells, it inhibited IL-9 production by CD49b+NKp46+ NK cells in mice. Furthermore, the enzyme-linked immunosorbent assay (ELISA) results showed that mouse NK cells could secrete mature IL-9 protein, and activin A inhibited IL-9 release by NK cells. Additionally, activin A inhibited interferon (IFN)-γ production in splenic NK cells in mice, but promoted IL-2 production, and did not alter the production of IL-10. Western blotting results showed that levels of activin type IIA receptor (ActRIIA), Smad3 and phosphorylated-Smad3 (p-SMAD3) protein increased in activin A-treated splenic NK cells, compared with that in control NK cells. The inhibitory effects of activin A on IL-9 production by NK cells were attenuated in the presence of activin antagonist follistatin (FST) or Smad3 knockdown to NK cells. These data suggest that although activin A up-regulates IL-9 expression in Th cells, it inhibits IL-9 production in NK cells through Smad3 signaling.
白细胞介素 9 (IL-9) 是 T 辅助 (Th)9 细胞分泌的细胞因子，激活素 A 可增强 Th9 细胞分化。然而，激活素 A 是否影响自然杀伤 (NK) 细胞产生 IL-9 尚不清楚。在此，我们发现不仅 Th 细胞，而且 Balb/c 小鼠的 CD3-CD49b+NKp46+NK 细胞也能产生 IL-9。虽然激活素 A 促进 CD4+Th 细胞中 IL-9 的表达，但它抑制了小鼠 CD49b+NKp46+NK 细胞中 IL-9 的产生。此外，酶联免疫吸附测定 (ELISA) 结果表明，小鼠 NK 细胞可以分泌成熟的 IL-9 蛋白，激活素 A 抑制 NK 细胞释放 IL-9。此外，激活素 A 抑制了小鼠脾 NK 细胞中干扰素 (IFN)-γ的产生，但促进了 IL-2 的产生，且不改变 IL-10 的产生。Western blot 结果表明，与对照组 NK 细胞相比，激活素 A 处理的脾 NK 细胞中激活素 IIA 型受体 (ActRIIA)、Smad3 和磷酸化-Smad3(p-SMAD3)蛋白的水平增加。在存在激活素拮抗剂滤泡抑制素 (FST) 或 NK 细胞中 Smad3 敲低的情况下，激活素 A 对 NK 细胞产生 IL-9 的抑制作用减弱。这些数据表明，尽管激活素 A 上调 Th 细胞中 IL-9 的表达，但它通过 Smad3 信号抑制 NK 细胞中 IL-9 的产生。
