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 TH17 subset of helper T cells and promoted angiogenesis. Interestingly, the ‘angio-lymphokine’ PlGF, in turn, specifically induced the differentiation of pathogenic TH17 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 TH17 differentiation, including experimental autoimmune encephalomyelitis and collagen-induced arthritis, in mice. Collectively, our findings provide insights into the PlGF-dictated links among angiogenesis, TH17 cell development and autoimmunity.
CITATION STYLE
Yoo, S. A., Kim, M., Kang, M. C., Kong, J. S., Kim, K. M., Lee, S., … Kim, W. U. (2019). Placental growth factor regulates the generation of TH17 cells to link angiogenesis with autoimmunity. Nature Immunology, 20(10), 1348–1359. https://doi.org/10.1038/s41590-019-0456-4
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