The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF.
The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF.
复制标题
作者：
产生白细胞介素17（IL - 17）的辅助性T细胞（TH17细胞）需要暴露于IL - 23才具有致脑炎作用，但是IL - 23促进其致病性的机制尚不清楚。在此我们发现IL - 23诱导TH17细胞产生细胞因子粒细胞巨噬细胞集落刺激因子（GM - CSF），并且GM - CSF在其致脑炎作用中起关键作用。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起重要作用的基础。IL - 23诱导了一个正反馈回路，即TH17细胞分泌的GM - CSF刺激抗原呈递细胞产生IL - 23。IL - 23和GM - CSF的这种相互调节解释了当这两种细胞因子中的任何一种缺失时对自身免疫的相似抵抗模式，并确定TH17细胞是自身免疫炎症中GM - CSF的关键来源。
Interleukin 17 (IL-17)-producing helper T cells (TH17 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 TH17 cells and that GM-CSF played 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 TH17 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 TH17 cells as a crucial source of GM-CSF in autoimmune inflammation.