C-type Lectin MCL Is an FcRγ-Coupled Receptor that Mediates the Adjuvanticity of Mycobacterial Cord Factor
C-type Lectin MCL Is an FcRγ-Coupled Receptor that Mediates the Adjuvanticity of Mycobacterial Cord Factor
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DOI：
10.1016/j.immuni.2013.03.010
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发表时间：
2013-05-23
期刊：
影响因子：
32.4
通讯作者：
Yamasaki, Sho
中科院分区：
文献类型：
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作者：
Miyake, Yasunobu;Toyonaga, Kenji;Yamasaki, Sho
脐带因子，也称为海藻糖-6，6 '-二霉菌酸酯（TDM），是一种有效的分枝杆菌佐剂。我们在此报告，C型凝集素MCL（也称为Clec 4d）是一种TDM受体，可能是由Mincle（也称为Clec 4 e）的基因复制引起的。已知Mincle是识别TDM的诱导型受体，而MCL在骨髓细胞中组成型表达。为了检查MCL对TDM佐剂的响应的贡献，我们产生了MCL缺陷小鼠。TDM促进先天性免疫反应，如肉芽肿形成，这是严重受损的MCL缺陷型小鼠。TDM诱导的获得性免疫反应，如实验性自身免疫性脑脊髓炎（EAE），几乎完全依赖于MCL，但不是Mincle。此外，通过产生Clec 4 e（gfp）报告小鼠，我们发现MCL对于驱动TDM刺激后的Mincle诱导也至关重要。这些结果表明，MCL是一个FcR γ-偶联激活受体介导的TDM的佐剂。
Cord factor, also called trehalose-6,6'-dimycolate (TDM), is a potent mycobacterial adjuvant. We herein report that the C-type lectin MCL (also called Clec4d) is a TDM receptor that is likely to arise from gene duplication of Mincle (also called Clec4e). Mincle is known to be an inducible receptor recognizing TDM, whereas MCL was constitutively expressed in myeloid cells. To examine the contribution of MCL in response to TDM adjuvant, we generated MCL-deficient mice. TDM promoted innate immune responses, such as granuloma formation, which was severely impaired in MCL-deficient mice. TDM-induced acquired immune responses, such as experimental autoimmune encephalomyelitis (EAE), was almost completely dependent on MCL, but not Mincle. Furthermore, by generating Clec4e(gfp) reporter mice, we found that MCL was also crucial for driving Mincle induction upon TDM stimulation. These results suggest that MCL is an FcR gamma-coupled activating receptor that mediates the adjuvanticity of TDM.