Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10
Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10
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DOI：
10.1038/ni.1772
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发表时间：
2009-09-01
影响因子：
30.5
通讯作者：
Rabinovich, Gabriel A.
中科院分区：
文献类型：
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作者：
Ilarregui, Juan M.;Croci, Diego O.;Rabinovich, Gabriel A.
尽管树突状细胞（DC）在协调免疫中起着重要作用，但它们可以通过致耐受性对抑制信号作出反应。在这里，我们表明，半乳糖凝集素-1，一种内源性聚糖结合蛋白，可以赋予DCs的耐受性潜力。在暴露于半乳糖凝集素-1后，DCs获得了白细胞介素27（IL-27）依赖的调节功能，促进IL-10介导的T细胞耐受并抑制自身免疫性神经炎症。与其调节功能一致，半乳糖凝集素-1在暴露于致耐受性刺激的DC上具有最高表达，并且从峰值到自身免疫病理学的消退是最丰富的。缺乏半乳糖凝集素-1的树突状细胞具有更大的免疫原性潜力，阻止炎症性疾病的能力受损。我们的研究结果确定了连接半乳糖凝集素-1信号传导、产生IL-27的DC和分泌IL-10的T细胞的致耐受性回路，这在免疫病理学中具有广泛的治疗意义。
Despite their central function in orchestrating immunity, dendritic cells (DCs) can respond to inhibitory signals by becoming tolerogenic. Here we show that galectin-1, an endogenous glycan-binding protein, can endow DCs with tolerogenic potential. After exposure to galectin-1, DCs acquired an interleukin 27 (IL-27)-dependent regulatory function, promoted IL-10-mediated T cell tolerance and suppressed autoimmune neuroinflammation. Consistent with its regulatory function, galectin-1 had its highest expression on DCs exposed to tolerogenic stimuli and was most abundant from the peak through the resolution of autoimmune pathology. DCs lacking galectin-1 had greater immunogenic potential and an impaired ability to halt inflammatory disease. Our findings identify a tolerogenic circuit linking galectin-1 signaling, IL-27-producing DCs and IL-10-secreting T cells, which has broad therapeutic implications in immunopathology.