The Glossopharyngeal Nerve in Neuroimmune Connections

描述(申请人提供)：口腔粘膜位于防御潜在感染的前线，扁桃体是次级淋巴器官，在启动对细菌和病毒抗原的免疫反应中发挥关键作用。众所周知，中枢神经系统可以调节免疫功能的几个方面。反过来，免疫细胞的产物可以向大脑发出信号，从而协调一系列系统和行为反应，统称为急性时相反应。在感染过程中，由抗原激活的免疫细胞释放的促炎细胞因子，通过在免疫和中枢神经系统之间提供双向信号，发挥着调节宿主防御反应的关键作用。神经传入参与了外周免疫信号向大脑的传递，我们已经证明舌咽传入是口腔后部的免疫挑战向大脑传递信息并引发中枢神经系统急性时相反应的神经通路。然而，舌咽神经免疫联系与大鼠口腔淋巴组织的解剖学特征仍有待阐明。我们的总体假设是舌咽神经调节大鼠鼻咽和腭部淋巴组织的免疫功能。第一个推论认为，舌咽神经为鼻咽淋巴组织的神经免疫连接提供了神经解剖学基础。第二个推论认为，舌咽神经传递鼻咽和腭部淋巴组织对局部免疫挑战的反应。第三个推论认为，鼻咽和腭部淋巴组织的局部免疫反应由舌咽神经调节。具体地说，我们的目标是：1)确定舌咽神经与鼻咽淋巴组织的神经解剖联系；2)确定舌咽神经对软腭部免疫攻击的反应；以及3)研究舌咽神经在调节鼻咽和腭部淋巴组织的局部免疫反应中的作用。这一途径的神经免疫特征应能深入了解口腔与局部炎症性疾病相关的病理生理学，包括口腔癌和粘膜疾病。

DESCRIPTION (provided by applicant): The oral mucosa is situated in the front line of defense against potential infections and the tonsils are secondary lymphoid organs that play a crucial role in initiating immune responses against bacterial and viral antigens. It is well established that the central nervous system can modulate several aspects of immune function. Reciprocally, products of immune cells can signal the brain and thereby coordinate a series of systemic and behavioral responses collectively known as the acute-phase response. During infection, proinflammatory cytokines released from antigen-activated immune cells, play a key role as regulators of the host defense response by providing bi-directional signals between the immune and the central nervous systems. The participation of neural afferents in the transmission of peripheral immune signals to the brain has been hypothesized and we have shown that glossopharyngeal afferents are the neural pathways by which immune challenge of the posterior oral cavity conveys information to the brain and elicits central nervous system manifestations of the acute-phase response. However, the anatomical characterization of the glossopharyngeal neuroimmune connection with lymphoid tissues in the oral cavity of the rat remains to be elucidated. Our overall hypothesis states that the glossopharyngeal nerve mediates the immune functions of the nasopharyngeal and palatine lymphoid tissues of the rat. The first corollary hypothesis states that glossopharyngeal innervation provides the neuroanatomical substrate for the neuroimmune connections of the nasopharyngeal lymphoid tissues. The second corollary hypothesis states that the glossopharyngeal nerves convey the response of nasopharyngeal and palatine lymphoid tissues to local immune challenge. The third corollary hypothesis states that the local immune response of nasopharyngeal and palatine lymphoid tissues is regulated by the glossopharyngeal nerves. Specifically, we aim to: 1) characterize the neuroanatomical connections of the glossopharyngeal nerves with the nasopharyngeal lymphoid tissues; 2) determine the response of the glossopharyngeal nerve to immune challenge of the soft palate; and 3) investigate the role of the glossopharyngeal nerve in regulating the local immune response of the nasopharyngeal and palatine lymphoid tissues. Neuroimmune characterization of this pathway should provide insight into the pathophysiology of the oral cavity related to local inflammatory diseases, including oral cancer and mucosal diseases.