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Placental growth factor regulates the generation of TH17 cells to link angiogenesis with autoimmunity

Yoo, SA;Kim, M;Kang, MC;Kong, JS;Kim, KM;Lee, S;Hong, BK;Jeong, GH;Lee, J;Shin, MG;Kim, YG;Apicella, I;Cicatiello, V;De Falco, S;Yoon, CH;Cho, CS;Ryoo, ZY;Lee, SH;Kim, WU;

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.