辅助性 T 细胞 17（T(H)17）细胞的致脑炎特性依赖于白细胞介素-1（IL-1）和白细胞介素-23（IL-23）诱导产生的细胞因子粒细胞-巨噬细胞集落刺激因子（GM-CSF）。
The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF.
机构信息
Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
出版信息
Nat Immunol. 2011 Jun;12(6):568-75. doi: 10.1038/ni.2031. Epub 2011 Apr 24.
Abstract
Interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) require exposure to IL-23 to become encephalitogenic, but the mechanism by which IL-23 promotes their pathogenicity is not known. Here we found that IL-23 induced production of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in T(H)17 cells and that GM-CSF had an essential role in their encephalitogenicity. Our findings identify a chief mechanism that underlies the important role of IL-23 in autoimmune diseases. IL-23 induced a positive feedback loop whereby GM-CSF secreted by T(H)17 cells stimulated the production of IL-23 by antigen-presenting cells. Such cross-regulation of IL-23 and GM-CSF explains the similar pattern of resistance to autoimmunity when either of the two cytokines is absent and identifies T(H)17 cells as a crucial source of GM-CSF in autoimmune inflammation.
摘要
白细胞介素 17（IL-17）-产生辅助性 T 细胞（T(H)17 细胞）需要暴露于 IL-23 才能成为致脑炎的，但 IL-23 促进其致病性的机制尚不清楚。在这里，我们发现 IL-23 诱导 T(H)17 细胞中细胞因子粒细胞-巨噬细胞集落刺激因子（GM-CSF）的产生，而 GM-CSF 在其致脑炎中起着至关重要的作用。我们的研究结果确定了一个主要机制，该机制是 IL-23 在自身免疫性疾病中发挥重要作用的基础。IL-23 诱导了正反馈回路，其中 T(H)17 细胞分泌的 GM-CSF 刺激抗原呈递细胞产生 IL-23。这种对 IL-23 和 GM-CSF 的交叉调节解释了两种细胞因子之一缺失时对自身免疫的相似抵抗模式，并确定 T(H)17 细胞是自身免疫炎症中 GM-CSF 的关键来源。
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