Sonderegger Ivo, Iezzi Giandomenica, Maier Reinhard, Schmitz Nicole, Kurrer Michael, Kopf Manfred
Institute of Integrative Biology, Molecular Biomedicine, ETH Zürich, 8952 Zürich, Switzerland.
J Exp Med. 2008 Sep 29;205(10):2281-94. doi: 10.1084/jem.20071119. Epub 2008 Sep 8.
Granulocyte macrophage-colony stimulating factor (GM-CSF) is critically involved in development of organ-related autoimmune inflammatory diseases including experimental allergic encephalitis and collagen-induced arthritis. Roles of GM-CSF in the initiation and in the effector phase of the autoimmune response have been proposed. Our study was designed to investigate the mechanisms of GM-CSF in autoimmunity using a model of autoimmune heart inflammatory disease (myocarditis). The pathological sequel after immunization with heart myosin has been shown previously to depend on IL-1, IL-6, IL-23, and IL-17. We found that innate GM-CSF was critical for IL-6 and IL-23 responses by dendritic cells and generation of pathological Th17 cells in vivo. Moreover, GM-CSF promoted autoimmunity by enhancing IL-6-dependent survival of antigen specific CD4(+) T cells. These results suggest a novel role for GM-CSF in promoting generation and maintenance of Th17 cells by regulation of IL-6 and IL-23 in vivo.
粒细胞巨噬细胞集落刺激因子（GM-CSF）在包括实验性变应性脑脊髓炎和胶原诱导性关节炎在内的器官相关自身免疫性炎性疾病的发展中起关键作用。GM-CSF在自身免疫反应的起始阶段和效应阶段所起的作用已被提出。我们的研究旨在利用自身免疫性心脏炎性疾病（心肌炎）模型来研究GM-CSF在自身免疫中的作用机制。先前已表明，用心脏肌球蛋白免疫后的病理后遗症取决于白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、白细胞介素-23（IL-23）和白细胞介素-17（IL-17）。我们发现，先天性GM-CSF对于树突状细胞的IL-6和IL-23反应以及体内病理性辅助性T细胞17（Th17细胞）的产生至关重要。此外，GM-CSF通过增强抗原特异性CD4(+) T细胞依赖IL-6的存活来促进自身免疫。这些结果表明，GM-CSF在体内通过调节IL-6和IL-23在促进Th17细胞的产生和维持方面具有新作用。
