Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity.
Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity.
复制标题
DOI：
10.1038/ncomms11273
复制
发表时间：
2016-04-12
影响因子：
16.6
通讯作者：
Sato K
中科院分区：
文献类型：
--
作者：
Uto T;Fukaya T;Takagi H;Arimura K;Nakamura T;Kojima N;Malissen B;Sato K
树突状细胞(DC)由几个亚群组成，它们在免疫的启动和调节中起着至关重要的作用。Clec4A4/DC免疫受体2(DCIR2)是一种C型凝集素受体，仅在CD8α−常规DC(CDCs)上表达。然而，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，我们表明，Clec4A4是一种调节受体，激活CD8α−CDC，从而损害炎症和T细胞免疫。Clec4a4、−/−、CD8、α−CDC在Toll样受体(Tlr)介导的活化后，细胞因子的产生和T细胞的启动增强。此外，Clec4a4−/−小鼠表现出TLR介导的过度炎症。在抗原免疫方面，Clec4a4−/−小鼠不仅表现出增强的T细胞反应，而且表现出进行性自身免疫发病。相反，Clec4a4−/−小鼠表现出对微生物感染的抵抗力，同时伴随着T细胞对微生物的增强反应。因此，我们的发现强调了Clec4A4在调节CD8CDC的功能以控制免疫反应的大小和质量中的作用。Clec4A4是CD8α−树突状细胞高表达的C型凝集素受体。在这里，作者表明，它的功能丧失导致T细胞反应增强和自身免疫加剧，暗示Clec4A4在限制CD8CD8α−树突状细胞的激活。
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. Clec4A4 is a C-type lectin receptor highly expressed by CD8α− dendritic cells. Here the authors show that its loss of function results in enhanced T cell responses and exacerbated autoimmunity, implicating Clec4A4 in limiting activation of the CD8α− dendritic cells.