Splenic Dendritic Cells Survey Red Blood Cells for Missing Self-CD47 to Trigger Adaptive Immune Responses.
Splenic Dendritic Cells Survey Red Blood Cells for Missing Self-CD47 to Trigger Adaptive Immune Responses.
复制标题
DOI：
10.1016/j.immuni.2015.08.021
复制
发表时间：
2015-10-20
期刊：
影响因子：
32.4
通讯作者：
Cyster JG
中科院分区：
文献类型：
--
作者：
Yi T;Li J;Chen H;Wu J;An J;Xu Y;Hu Y;Lowell CA;Cyster JG
绵羊红细胞（SRBC）长期以来一直被用作引发全身免疫应答的模型抗原，但其佐剂活性的基础尚不清楚。在这里，我们发现SRBC不能与脾脏CD 4+树突状细胞（DC）上的抑制性小鼠SIRPα受体结合，这导致DC活化。从自身RBC中去除SIRPα配体CD 47足以将其转化为适应性免疫应答的佐剂。DC对Cd 47 −/− RBC的捕获和DC活化在几分钟内以src家族激酶和CD 18整合素依赖性方式发生。这些发现为SRBC的佐剂机制提供了解释，并揭示了脾脏DC对血细胞中缺失的自身CD 47进行调查，这一过程可能有助于检测和建立针对病原体感染的RBC的免疫应答。
Sheep red blood cells (SRBCs) have long been used as a model antigen for eliciting systemic immune responses yet the basis for their adjuvant activity has been unknown. Here we show that SRBCs failed to engage the inhibitory mouse SIRPα receptor on splenic CD4+ dendritic cells (DCs), and this led to DC activation. Removal of the SIRPα ligand, CD47, from self-RBCs was sufficient to convert them into an adjuvant for adaptive immune responses. DC capture of Cd47−/− RBCs and DC activation occurred within minutes in a src-family kinase and CD18 integrin-dependent manner. These findings provide an explanation for the adjuvant mechanism of SRBCs and reveal that splenic DCs survey blood cells for missing self-CD47, a process that may contribute to detecting and mounting immune responses against pathogen-infected RBCs.