Spleen glia in autonomic regulation of immunity

项目摘要。 应激强烈影响免疫系统，特别是抗原特异的适应性免疫反应，通过 交感神经流出和肾上腺素能受体的激活。然而，尽管有一致的发现 交感神经递质肾上腺素和去甲肾上腺素调节抗原提呈细胞和T细胞 和B淋巴细胞通过肾上腺素能受体，结果取决于上下文-要么激活，要么 观察到对抗原依赖反应的抑制。重要的是，调解这些对立的线索 其影响还没有被很好地理解。我们建议在这里生成工具来了解脾胶质细胞是否在 交感神经流出对适应性免疫的影响在调节这些上下文相关效应中的作用尚不清楚。 携带肾上腺素能神经递质的交感神经末梢进入脾的动脉供血周围 并支配白髓，在那里抗原特异的T和B淋巴细胞反应持续 发展中的。因此，伴随交感神经的胶质细胞处于影响应激效应的最佳位置。 依赖抗原的获得性免疫反应。然而，测试这一点的障碍是脾胶质细胞 以前都没有被描述过。因此，我们正在申请R21资金来描述它们的解剖结构和 翻译组(翻译mRNAs)，并确定它们是否在 严重中风时的极端生理应激。在这些实验的结论中，我们将产生 工具不仅研究脾胶质细胞，而且还研究其他外周神经胶质细胞，并已确定脾胶质细胞 是交感神经介导的免疫反应效应的重要参与者。这些研究是 适合R21资助，因为它们是一个新科学领域的高风险初始研究，即 脾神经胶质细胞的功能。

Project Summary. Stress strongly influences the immune system, particularly antigen-specific adaptive immune responses, via sympathetic outflow and activation of adrenergic receptors. However, although there are consistent findings that the sympathetic neurotransmitters epinephrine and norepinephrine regulate antigen presenting cells and T and B lymphocytes via adrenergic receptors, the results are context dependent–either activation or suppression of antigen-dependent responses is observed. Importantly, the cues that mediate these opposing effects are not well understood. We propose here to generate tools to understand whether spleen glia play an unrecognized role in regulating these context-dependent effects of sympathetic outflow on adaptive immunity. Sympathetic terminals carrying adrenergic neurotransmitters enter the spleen around the arterial blood supply and innervate the white pulp, where antigen-specific T and B lymphocyte responses are continually developing. So glia accompanying the sympathetic nerves are optimally positioned to influence stress effects on antigen-dependent adaptive immune responses. The barrier to testing this is, however, that spleen glia have not previously been described. We are therefore requesting R21 funding to describe their anatomy and translatome (translating mRNAs), and to determine if they change their expression of immune genes during the extreme physiological stress of a large stroke. At the conclusion of these experiments, we will have generated tools to study not only spleen glia, but also other peripheral glia, and also have established whether spleen glia are important participants in sympathetically-mediated effects on immune responses. These studies are appropriate for R21 funding as they are high-risk initial studies in a new scientific area, the study of the functions of spleen glia.