Dendritic cells (DCs) comprise several subsets that are critically involved in the initiation and regulation of immunity. Clec4A4/DC immunoreceptor 2 (DCIR2) is a C-type lectin receptor (CLR) exclusively expressed on CD8α(-) conventional DCs (cDCs). However, how Clec4A4 controls immune responses through regulation of the function of CD8α(-) cDCs remains unclear. Here we show that Clec4A4 is a regulatory receptor for the activation of CD8α(-) cDCs that impairs inflammation and T-cell immunity. Clec4a4(-/-)CD8α(-) cDCs show enhanced cytokine production and T-cell priming following Toll-like receptor (TLR)-mediated activation. Furthermore, Clec4a4(-/-) mice exhibit TLR-mediated hyperinflammation. On antigenic immunization, Clec4a4(-/-) mice show not only augmented T-cell responses but also progressive autoimmune pathogenesis. Conversely, Clec4a4(-/-) mice exhibit resistance to microbial infection, accompanied by enhanced T-cell responses against microbes. Thus, our findings highlight roles of Clec4A4 in regulation of the function of CD8α(-) cDCs for control of the magnitude and quality of immune response.

中文翻译：

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Clec4A4是树突状细胞的调节性受体，可削弱炎症和T细胞免疫力。

树突状细胞（DC）包含几个重要的子集，这些子集与免疫的启动和调节密切相关。Clec4A4 / DC免疫受体2（DCIR2）是仅在CD8α（-）常规DC（cDC）上表达的C型凝集素受体（CLR）。但是，Clec4A4如何通过调节CD8α（-）cDC的功能来控制免疫反应仍不清楚。在这里，我们显示Clec4A4是CD8α（-）cDC激活的调节受体，可削弱炎症和T细胞免疫力。Clec4a4（-/-）CD8α（-）cDCs在Toll样受体（TLR）介导的激活后显示增强的细胞因子产生和T细胞启动。此外，Clec4a4（-/-）小鼠表现出TLR介导的过度炎症。在抗原免疫上，Clec4a4（-/-）小鼠不仅显示出增强的T细胞反应，还显示出进行性自身免疫性发病机制。反过来，Clec4a4（-/-）小鼠表现出对微生物感染的抵抗力，并伴随着增强的T细胞对微生物的反应。因此，我们的发现突出了Clec4A4在调节CD8α（-）cDC的功能中的作用，以控制免疫应答的大小和质量。