Apoptotic cells mediate the development of tolerogenic dendritic cells (DC) and thus facilitate induction and maintenance of peripheral tolerance. Following the identification of the evolutionary conserved annexin core domain (Anx) as a specific signal on apoptotic cells which antagonises Toll-like receptor (TLR) signalling, we examined whether the tolerogenic capacity of Anx can be exploited to downregulate antigen-specific immune responses. The treatment of bone marrow-derived dendritic cells (BMDC) with particles harbouring Anx as well as the model antigen ovalbumin (OVA) attenuated the response of OVA-specific OT-II T cells. The co-culture of Anx-particle-treated DC and T cells resulted in an anergy-like phenotype characterized by reduced proliferation and cytokine secretion. Here we demonstrate that the anti-inflammatory effects of Anx which are mediated through DC can be used as a tool to generate a particle-based antigen delivery system that promotes antigen-specific immunosuppression. Such Anx-particles may be a new therapeutic approach for the treatment of autoimmune diseases.

中文翻译：

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膜联蛋白包被的颗粒诱导抗原特异性免疫抑制。

凋亡细胞介导耐受性树突状细胞（DC）的发展，从而促进诱导和维持外周耐受。在确定进化保守保守的膜联蛋白核心结构域（Anx）作为凋亡细胞上的一种特异性信号后，该细胞拮抗Toll样受体（TLR）信号转导，我们检查了Anx的致耐受能力是否可以用来下调抗原特异性免疫反应。带有Anx颗粒和模型抗原卵清蛋白（OVA）的颗粒对骨髓源性树突状细胞（BMDC）的处理减弱了OVA特异性OT-II T细胞的应答。经Anx颗粒处理的DC和T细胞的共培养导致了类似无反应的表型，其特征是增殖和细胞因子分泌减少。在这里，我们证明了通过DC介导的Anx的抗炎作用可以用作生成基于颗粒的抗原递送系统的工具，该系统可促进抗原特异性免疫抑制。此类Anx颗粒可能是治疗自身免疫性疾病的新治疗方法。