Development of Immunologic therapies against uveitis

对I27-Breg细胞免疫抑制作用机制的研究导致我们发现I27-Breg细胞分泌含有IL-27的外切体(I27-exosome)。过继转移I27-exosome通过拮抗Th1/Th17反应，上调与T细胞耗竭相关的抑制受体，同时诱导Treg扩张，从而抑制小鼠的葡萄膜炎。因此，使用I27-exosome避免了IL-27的剂量问题，使确定治疗所需的生物可利用的异二聚体IL-27成为可能。此外，由于外切体很容易通过血-视网膜屏障，而且用I27-外切体治疗的小鼠没有不良反应，本研究结果表明，I27-外切体可能是治疗中枢神经系统自身免疫性疾病的一种有前途的方法。

Studies to understand mechanisms underlying the immune suppressive effects of i27-Breg cells led to our discovery that i27-Breg cells secrete IL-27-containing exosomes (i27-exosomes). Adoptive transfer of the i27-exosomes suppressed uveitis in mice by antagonizing Th1/Th17 responses, upregulating inhibitory-receptors associated with T-cell exhaustion while inducing Treg expansion. Use of i27-exosomes thus obviates the IL-27 dosing problem, making it possible to determine bioavailable heterodimeric IL-27 needed for therapy. Moreover, as exosomes readily cross the blood-retina-barrier and no adverse effects were observed in mice treated with i27-exosome, results of this study suggest that i27-exosomes might be a promising therapeutic approach for CNS autoimmune diseases.