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用与皂草素毒素偶联的抗CD209耗尽炎性树突状细胞。

Depletion of inflammatory dendritic cells with anti-CD209 conjugated to saporin toxin.

作者信息

Alonso Michael N, Gregorio Josh G, Davidson Matthew G, Gonzalez Joseph C, Engleman Edgar G

机构信息

Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.

出版信息

Immunol Res. 2014 May;58(2-3):374-7. doi: 10.1007/s12026-014-8511-6.

Abstract

Monocytes rapidly infiltrate inflamed tissues and differentiate into CD209(+) inflammatory dendritic cells (DCs) that promote robust immunity or, if unregulated, inflammatory disease. Previous studies in experimental animal models indicate that inflammatory DC depletion through systemic elimination of their monocyte precursors with clodronate-loaded liposomes ameliorates the development of psoriasis and other diseases. However, translation of systemic monocyte depletion strategies is difficult due to the importance of monocytes during homeostasis and infection clearance. Here, we describe a strategy that avoids the monocyte intermediates to deplete inflammatory DCs through antibody-loaded toxin. Mice with an abundance of inflammatory DCs as a consequence of lipopolysaccharide exposure were treated with anti-CD209 antibody conjugated to saporin, a potent ribosome inactivator. The results demonstrate depletion of CD209(+) DCs. This strategy could prove useful for the targeted reduction of inflammatory DCs in disease.

摘要

单核细胞迅速浸润炎症组织并分化为CD209(+)炎性树突状细胞(DCs),这些细胞可促进强大的免疫反应,但若不受调控,则会引发炎性疾病。先前在实验动物模型中的研究表明,通过用载有氯膦酸盐的脂质体系统性清除炎性DCs的单核细胞前体来减少炎性DCs,可改善银屑病和其他疾病的发展。然而,由于单核细胞在体内稳态和感染清除过程中的重要性,系统性单核细胞耗竭策略的转化应用存在困难。在此,我们描述了一种策略,该策略通过负载抗体的毒素避免单核细胞中间体来耗尽炎性DCs。用与皂草素(一种有效的核糖体失活剂)偶联的抗CD209抗体处理因暴露于脂多糖而富含炎性DCs的小鼠。结果表明CD209(+) DCs被耗尽。该策略可能对疾病中炎性DCs的靶向减少有用。

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