α7 Nicotinic Acetylcholine Receptor (α7nAChR) Expression in Bone Marrow-Derived Non-T Cells Is Required for the Inflammatory Reflex
α7 Nicotinic Acetylcholine Receptor (α7nAChR) Expression in Bone Marrow-Derived Non-T Cells Is Required for the Inflammatory Reflex
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DOI：
10.2119/molmed.2011.00405
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发表时间：
2012-03-01
影响因子：
5.7
通讯作者：
Chavan, Sangeeta S.
中科院分区：
文献类型：
--
作者：
Olofsson, Peder S.;Katz, David A.;Chavan, Sangeeta S.
对感染或损伤的免疫反应协调宿主防御和组织修复，但也具有损伤宿主组织的能力。在了解保护机制方面的最新进展发现，神经回路可以抑制破坏性细胞因子的释放。刺激迷走神经可防止细胞因子过度产生并改善实验性炎症性疾病。这种机制（炎症反射）需要 α7 烟碱乙酰胆碱受体 (α7nAChR)，这是一种在巨噬细胞、淋巴细胞、神经元和其他细胞上表达的配体门控离子通道。为了研究 α 7nAChR 在炎症反射中的细胞特异性功能，我们通过在野生型 (WT) 和 α 7nAChR 缺陷型小鼠之间交叉转移骨髓来创建嵌合小鼠。骨髓源性细胞中α7nAChR的缺乏会显着损害迷走神经介导的肿瘤坏死因子（TNF）的调节，而神经元和其他细胞中α7nAChR的缺乏则没有显着影响。与最近的研究一致，炎症反射在裸鼠中不起作用，因为功能性 T 细胞是该通路完整性所必需的。为了研究 T 细胞 α 7nAChR 的作用，我们将 α 7nAChR 缺陷细胞或 WIT 细胞过继转移至裸鼠体内。 WT 和 α 7nAChR 缺陷型 T 细胞的转移恢复了功能，表明 T 细胞上的 α 7nAChR 表达对于该途径不是必需的。 总之，这些结果表明骨髓来源的非 T 细胞中的 α 7nAChR 表达对于炎症反射的完整性是必需的。在线地址：http://www.molmed.org doi:10.2119/molmed.2011.00405
The immune response to infection or injury coordinates host defense and tissue repair, but also has the capacity to damage host tissues. Recent advances in understanding protective mechanisms have found neural circuits that suppress release of damaging cytokines. Stimulation of the vagus nerve protects from excessive cytokine production and ameliorates experimental inflammatory disease, This mechanism, the inflammatory reflex, requires the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR), a ligand-gated ion channel expressed on macrophages, lymphocytes, neurons and other cells. To investigate cell-specific function of alpha 7nAChR in the inflammatory reflex, we created chimeric mice by cross-transferring bone marrow between wild-type (WT) and alpha 7nAChR-deficient mice. Deficiency of alpha 7nAChR in bone marrow-derived cells significantiy impaired vagus nerve-mediated regulation of tumor necrosis factor (TNF), whereas alpha 7nAChR deficiency in neurons and other cells had no significant effect. In agreement with recent work, the inflammatory reflex was not functional in nude mice, because functional T cells are required for the integrity of the pathway. To investigate the role of T-cell alpha 7nAChR, we adoptively transferred alpha 7nAChR-deficient or WIT cells to nude mice. Transfer of WT and alpha 7nAChR-deficient T cells restored function, indicating that alpha 7nAChR expression on T cells is not necessary for this pathway, Together, these results indicate that alpha 7nAChR expression in bone marrow-derived non-T cells is required for the integrity of the inflammatory reflex. Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00405