Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, Korea.
Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Korea.
Nat Immunol. 2019 Oct;20(10):1348-1359. doi: 10.1038/s41590-019-0456-4. Epub 2019 Aug 12.
Helper T cells actively communicate with adjacent cells by secreting soluble mediators, yet crosstalk between helper T cells and endothelial cells remains poorly understood. Here we found that placental growth factor (PlGF), a homolog of the vascular endothelial growth factor that enhances an angiogenic switch in disease, was selectively secreted by the T17 subset of helper T cells and promoted angiogenesis. Interestingly, the 'angio-lymphokine' PlGF, in turn, specifically induced the differentiation of pathogenic T17 cells by activating the transcription factor STAT3 via binding to its receptors and replaced the activity of interleukin-6 in the production of interleukin-17, whereas it suppressed the generation of regulatory T cells. Moreover, T cell-derived PlGF was required for the progression of autoimmune diseases associated with T17 differentiation, including experimental autoimmune encephalomyelitis and collagen-induced arthritis, in mice. Collectively, our findings provide insights into the PlGF-dictated links among angiogenesis, T17 cell development and autoimmunity.
辅助性 T 细胞通过分泌可溶性介质与相邻细胞主动交流，但辅助性 T 细胞与内皮细胞之间的串扰仍知之甚少。在这里，我们发现胎盘生长因子（PlGF）是血管内皮生长因子的同源物，可增强疾病中的血管生成开关，选择性地由辅助性 T 细胞的 T17 亚群分泌，并促进血管生成。有趣的是，这种“血管淋巴管因子”PlGF 通过与其受体结合激活转录因子 STAT3，反过来又特异性诱导致病性 T17 细胞的分化，从而取代白细胞介素-6 在白细胞介素-17 产生中的作用，而抑制调节性 T 细胞的产生。此外，T 细胞衍生的 PlGF 是与 T17 分化相关的自身免疫性疾病进展所必需的，包括实验性自身免疫性脑脊髓炎和胶原诱导性关节炎。总之，我们的研究结果为 PlGF 决定的血管生成、T17 细胞发育和自身免疫之间的联系提供了新的见解。
