TLT2 Potentiates Neutrophil Antibacterial Activity and Chemotaxis in Response to G Protein-Coupled Receptor-Mediated Signaling
TLT2 Potentiates Neutrophil Antibacterial Activity and Chemotaxis in Response to G Protein-Coupled Receptor-Mediated Signaling
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DOI：
10.4049/jimmunol.1100534
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发表时间：
2011-09-01
影响因子：
4.4
通讯作者：
Justement, Louis B.
中科院分区：
文献类型：
--
作者：
Halpert, Matthew M.;Thomas, Kimberly A.;Justement, Louis B.
已显示Trem基因座内编码的受体在调节对模式识别受体信号传导的细胞应答中起重要作用。TREM样转录物2（TLT 2）是Trem基因座的成员，其在小鼠和人中是保守的。TLT 2表现出独特的表达模式，因为它在骨髓和淋巴谱系的细胞上表达，这表明它在先天性和适应性免疫中起作用。在这项工作中，研究表明TLT 2在增强中性粒细胞抗菌活性和趋化性中起重要作用。TLT 2连接增强中性粒细胞对甲酰化肽FMLF的反应，导致活性氧产生、脱粒和趋化性增加。此外，TLT 2具有响应于一系列结合G蛋白偶联受体的激动剂而特异性增强中性粒细胞活化和趋化性的能力，因为它不增强细胞对生长因子受体、Fc受体或TLR介导的信号传导的响应。最后，TLT 2连接增强了中性粒细胞在体内炎症部位的募集。这些发现揭示了TLT 2的一种新的功能作用，涉及增强中性粒细胞对G蛋白偶联受体信号的反应。因此，TLT 2似乎通过一种新的分子机制在增强先天免疫应答中发挥重要作用。免疫学杂志，2011，187：2346-2355。
Receptors encoded within the Trem locus have been shown to play an important role in modulating the cellular response to pattern recognition receptor signaling. TREM-like transcript 2 (TLT2) is a member of the Trem locus that is conserved in mouse and human. TLT2 exhibits a unique expression pattern in that it is expressed on cells of the myeloid and lymphoid lineage, suggesting that it plays a role in both innate and adaptive immunity. In this work, studies reveal that TLT2 plays an important role in potentiating neutrophil antibacterial activity and chemotaxis. TLT2 ligation enhances the neutrophil response to the formylated peptide FMLF, leading to increased reactive oxygen species production, degranulation, and chemotaxis. Moreover, TLT2 has the ability to specifically potentiate neutrophil activation and chemotaxis in response to a range of agonists that bind to G protein-coupled receptors, as it does not potentiate the response of cells to growth factor receptor-, Fc receptor-, or TLR-mediated signaling. Finally, TLT2 ligation potentiates the recruitment of neutrophils to sites of inflammation in vivo. These findings reveal a novel functional role for TLT2 that involves potentiation of neutrophil responses to G protein-coupled receptor signaling. Thus, TLT2 appears to play an important role in enhancing the innate immune response via a novel molecular mechanism. The Journal of Immunology, 2011, 187: 2346-2355.