Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, UK.
Eur J Immunol. 2011 Oct;41(10):3040-53. doi: 10.1002/eji.201141641. Epub 2011 Aug 17.
Myeloid cells express a plethora of C-type lectin receptors (CLRs) that can regulate immune responses. CLEC-2 belongs to the Dectin-1 sub-family of CLRs that possess an extracellular C-type lectin-like domain and a single intracellular hemITAM motif. CLEC-2 is highly expressed on mouse and human platelets where it signals via Syk to promote aggregation. We generated a monoclonal antibody (mAb) against mouse CLEC-2 and found that CLEC-2 is additionally widely expressed on leukocytes and that its expression is upregulated during inflammation. MAb-mediated crosslinking of CLEC-2 leads to hemITAM-dependent signaling via Syk, Ca(2+) and NFAT and, in myeloid cells, modulates the effect of toll-like receptor (TLR) agonists to selectively potentiate production of IL-10. A macrophage/dendritic cell-dependent increase in IL-10 is also observed in mice given anti-CLEC-2 mAb together with LPS. Collectively, these data indicate that CLEC-2 is expressed in myeloid cells and acts as a Syk-coupled CLR able to modulate TLR signaling and inflammatory responses.
髓样细胞表达大量 C 型凝集素受体 (CLRs)，可调节免疫反应。CLEC-2 属于 Dectin-1 型 CLR 亚家族，具有细胞外 C 型凝集素样结构域和单个细胞内 hemITAM 基序。CLEC-2 在小鼠和人血小板上高度表达，通过 Syk 信号促进聚集。我们生成了一种针对小鼠 CLEC-2 的单克隆抗体 (mAb)，并发现 CLEC-2 还广泛表达于白细胞上，其表达在炎症期间上调。CLEC-2 的 mAb 交联导致 Syk、Ca(2+) 和 NFAT 依赖的 hemITAM 信号转导，并且在髓样细胞中，调节 Toll 样受体 (TLR) 激动剂的作用以选择性增强 IL-10 的产生。在给予抗 CLEC-2 mAb 加 LPS 的小鼠中，还观察到巨噬细胞/树突状细胞依赖性的 IL-10 增加。总之，这些数据表明 CLEC-2 在髓样细胞中表达，并作为一种能够调节 TLR 信号和炎症反应的 Syk 偶联 CLR。
