Enhanced Dendritic Cell-Induced Immune Responses Mediated by the Novel C-Type Lectin Receptor mDCAR1
Enhanced Dendritic Cell-Induced Immune Responses Mediated by the Novel C-Type Lectin Receptor mDCAR1
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DOI：
10.4049/jimmunol.0900908
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发表时间：
2009-10-15
影响因子：
4.4
通讯作者：
Winkels, Gregor
中科院分区：
文献类型：
--
作者：
Kaden, Stefan A.;Kurig, Stefanie;Winkels, Gregor
树突状细胞 (DC) 免疫受体 (DCIR) 和 DC 免疫激活受体 (DCAR) 代表细胞表面 C 型凝集素受体 (CLR) 的一个亚家族，其多功能能力范围从经典的 Ag 摄取和免疫调节机制到参与 DC 个体发育。在产生特定 mAb 的基础上，我们对小鼠 DCAR1 (mDCAR1) 进行了功能表征，将其视为 DCIR/DCAR 家族的成员。 mDCAR1 的表达具有强烈的组织依赖性。 mDCAR1在DC上的表达仅限于脾脏和胸腺中的CD8（+）DC亚群以及骨髓和脾脏中的CD11b（+）骨髓细胞亚群，而在淋巴结和外周血中的两种细胞类型中均未检测到该分子。就 CLR 作为模式识别受体的功能而言，通过 mDCAR1 传递的 Ag 被内化，被运输到早期和晚期内体/溶酶体，因此，即使在没有 CD40 刺激的情况下，也会在体内诱导细胞和不道德反应。有趣的是，在触发 mDCAR1 后，CD8+ DC 增加了生物活性 IL-12 的分泌，而 IL-10 的释放显着减少，从而表明 mDCAR1 识别的 Ag 诱导增强的促炎反应。这些数据表明 mDCAR1 是免疫系统细胞上的功能性受体，并为 CLR 调节免疫反应提供了进一步的见解。免疫学杂志，2009，183：5069-5078。
The dendritic cell (DC) immunoreceptors (DCIR) and DC-immunoactivating receptors (DCAR) represent a subfamily of cell surface C-type lectin receptors (CLR), whose multifunctional capacities range from classical Ag uptake and immunoregulatory mechanisms to the involvement in DC ontogeny. On the basis of the generation of specific mAbs, we functionally characterized mouse DCAR1 (mDCAR1) as a member of the DCIR/DCAR family. Expression of mDCAR1 was strongly tissue dependent. mDCAR1 expression on DCs was restricted to the CD8(+) DC subset in spleen and thymus and on subpopulations of CD11b(+) myeloid cells in bone marrow and spleen, whereas the molecule was not detectable on both cell types in lymph nodes and peripheral blood. With respect to the function of CLRs as pattern recognition receptors, Ag delivered via mDCAR1 was internalized, was trafficked to early and late endosomes/lysosomes and, as a consequence, induced cellular and Immoral responses in vivo even in the absence of CD40 stimulation. Intriguingly, upon triggering mDCAR1, CD8(+) DCs increased the secretion of bioactive IL-12, whereas IL-10 release is markedly reduced, thereby indicating that Ag recognized by mDCAR1 induces enhanced proinflammatory responses. These data indicate that mDCAR1 is a functional receptor on cells of the immune system and provides further insights into the regulation of immune responses by CLRs. The Journal of Immunology, 2009, 183: 5069-5078.