Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Immunol. 2010 Feb 15;184(4):1776-83. doi: 10.4049/jimmunol.0901843. Epub 2010 Jan 18.
Previous studies have implicated T cell production of IL-17 in resistance to Toxoplasma gondii as well as the development of immune-mediated pathology during this infection. Analysis of C57BL/6 and C57BL/6 RAG(-/-) mice challenged with T. gondii-identified NK cells as a major innate source of IL-17. The ability of soluble Toxoplasma Ag to stimulate NK cells to produce IL-17 was dependent on the presence of accessory cells and the production of IL-6, IL-23, and TGF-beta. In contrast, these events were inhibited by IL-2, IL-15, and IL-27. Given that IL-6 was one of the most potent enhancers of NK cell production of IL-17, further studies revealed that only a subset of NK cells expressed both chains of the IL-6R, IL-6 upregulated expression of the Th17-associated transcription factor RORgammat, and that IL-6(-/-) mice challenged with T. gondii had a major defect in NK cell production of IL-17. Together, these data indicate that many of the same cytokines that regulate Th17 cells are part of a conserved pathway that also control innate production of IL-17 and identify a major role for IL-6 in the regulation of NK cell responses.
先前的研究表明，T 细胞产生的白细胞介素-17（IL-17）在抵抗刚地弓形虫以及在感染过程中产生免疫介导的病理中起作用。对感染刚地弓形虫的 C57BL/6 和 C57BL/6 RAG(-/-) 小鼠进行分析，发现 NK 细胞是 IL-17 的主要先天来源。可溶性弓形虫抗原刺激 NK 细胞产生 IL-17 的能力依赖于辅助细胞的存在和白细胞介素-6（IL-6）、白细胞介素-23（IL-23）和转化生长因子-β（TGF-β）的产生。相比之下，这些事件受到白细胞介素-2（IL-2）、白细胞介素-15（IL-15）和白细胞介素-27（IL-27）的抑制。鉴于 IL-6 是增强 NK 细胞产生 IL-17 的最有效因子之一，进一步的研究表明，只有一部分 NK 细胞表达 IL-6R 的两条链，IL-6 上调了 Th17 相关转录因子 RORgammat 的表达，并且 IL-6(-/-) 感染弓形虫的小鼠在 NK 细胞产生 IL-17 方面存在重大缺陷。这些数据表明，许多调节 Th17 细胞的细胞因子也是控制先天产生 IL-17 的保守途径的一部分，并确定 IL-6 在调节 NK 细胞反应中起着重要作用。
