Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells.
Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells.
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DOI：
10.1182/blood-2007-04-085787
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发表时间：
2008-01
期刊：
影响因子：
20.3
通讯作者：
Y. Yamanishi;J. Kitaura;Kumi Izawa;T. Matsuoka;T. Oki;Yang Lu;F. Shibata;S. Yamazaki;H. Kumagai;H. Nakajima;M. Maeda-Yamamoto;V. Tybulewicz;T. Takai;T. Kitamura
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文献类型：
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作者：
Y. Yamanishi;J. Kitaura;Kumi Izawa;T. Matsuoka;T. Oki;Yang Lu;F. Shibata;S. Yamazaki;H. Kumagai;H. Nakajima;M. Maeda-Yamamoto;V. Tybulewicz;T. Takai;T. Kitamura
我们分析了白细胞单免疫球蛋白样受体5（LMIR 5）作为一个激活受体之间配对LMIRs。小鼠LMIR 5（mLMIR 5）在骨髓细胞如肥大细胞、粒细胞、巨噬细胞和树突细胞中表达。骨髓来源的肥大细胞（BMMC）中转导的mLMIR 5的交联引起活化事件，包括细胞因子产生、细胞存活、脱粒和粘附至细胞外基质。mLMIR 5与DAP 12相关，在较小程度上与DAP 10相关，并且DAP 12缺陷强烈抑制mLMIR 5介导的BMMC功能。重要的是，内源性mLMIR 5的交联诱导Syk依赖性激活胎肝来源的肥大细胞。与mLMIR 5不同，人LMIR 5（hLMIR 5）的交联即使在不存在DAP 12和DAP 10的情况下也诱导BMMC的细胞因子产生，这表明存在未鉴定的衔接子。有趣的是，hLMIR 5在胞质区域具有酪氨酸残基（Y188）。通过Y188磷酸化的信号传导在DAP 12缺陷的但不是野生型BMMC中的hLMIR 5介导的细胞因子产生中起主要作用。此外，使用DAP 10/DAP 12双缺陷BMMC的实验表明存在来自未鉴定的衔接子的Y188磷酸化依赖性和非依赖性信号。总的来说，尽管小鼠和人LMIR 5在先天免疫细胞中均发挥激活作用，但LMIR 5的功能在小鼠细胞与人细胞中受到差异调节。
We have analyzed leukocyte mono-Ig-like receptor 5 (LMIR5) as an activating receptor among paired LMIRs. Mouse LMIR5 (mLMIR5) is expressed in myeloid cells such as mast cells, granulocytes, macrophages, and dendritic cells. Cross-linking of transduced mLMIR5 in bone marrow-derived mast cells (BMMCs) caused activation events, including cytokine production, cell survival, degranulation, and adhesion to the extracellular matrix. mLMIR5 associated with DAP12 and to a lesser extent with DAP10, and mLMIR5-mediated functions of BMMCs were strongly inhibited by DAP12 deficiency. Importantly, cross-linking of endogenous mLMIR5 induced Syk-dependent activation of fetal liver-derived mast cells. Unlike mLMIR5, cross-linking of human LMIR5 (hLMIR5) induced cytokine production of BMMCs even in the absence of both DAP12 and DAP10, suggesting the existence of unidentified adaptors. Interestingly, hLMIR5 possessed a tyrosine residue (Y188) in the cytoplasmic region. Signaling via Y188 phosphorylation played a predominant role in hLMIR5-mediated cytokine production in DAP12-deficient, but not wild-type BMMCs. In addition, experiments using DAP10/DAP12 double-deficient BMMCs suggested the existence of Y188 phoshorylation-dependent and -independent signals from unidentified adaptors. Collectively, although both mouse and human LMIR5 play activatory roles in innate immunity cells, the functions of LMIR5 were differentially regulated in mouse versus human cells.