Voisin Tiphaine, Bouvier Amélie, Chiu Isaac M
Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Int Immunol. 2017 Jun 1;29(6):247-261. doi: 10.1093/intimm/dxx040.
Recent studies have highlighted an emerging role for neuro-immune interactions in mediating allergic diseases. Allergies are caused by an overactive immune response to a foreign antigen. The peripheral sensory and autonomic nervous system densely innervates mucosal barrier tissues including the skin, respiratory tract and gastrointestinal (GI) tract that are exposed to allergens. It is increasingly clear that neurons actively communicate with and regulate the function of mast cells, dendritic cells, eosinophils, Th2 cells and type 2 innate lymphoid cells in allergic inflammation. Several mechanisms of cross-talk between the two systems have been uncovered, with potential anatomical specificity. Immune cells release inflammatory mediators including histamine, cytokines or neurotrophins that directly activate sensory neurons to mediate itch in the skin, cough/sneezing and bronchoconstriction in the respiratory tract and motility in the GI tract. Upon activation, these peripheral neurons release neurotransmitters and neuropeptides that directly act on immune cells to modulate their function. Somatosensory and visceral afferent neurons release neuropeptides including calcitonin gene-related peptide, substance P and vasoactive intestinal peptide, which can act on type 2 immune cells to drive allergic inflammation. Autonomic neurons release neurotransmitters including acetylcholine and noradrenaline that signal to both innate and adaptive immune cells. Neuro-immune signaling may play a central role in the physiopathology of allergic diseases including atopic dermatitis, asthma and food allergies. Therefore, getting a better understanding of these cellular and molecular neuro-immune interactions could lead to novel therapeutic approaches to treat allergic diseases.
最近的研究强调了神经免疫相互作用在介导过敏性疾病中所起的新作用。过敏是由对外来抗原的过度活跃的免疫反应引起的。外周感觉和自主神经系统密集地支配着包括皮肤、呼吸道和胃肠道等暴露于过敏原的黏膜屏障组织。越来越清楚的是，在过敏性炎症中，神经元积极地与肥大细胞、树突状细胞、嗜酸性粒细胞、Th2细胞和2型固有淋巴细胞进行交流并调节其功能。已经发现了这两个系统之间相互作用的几种机制，且可能具有解剖学特异性。免疫细胞释放包括组胺、细胞因子或神经营养因子在内的炎症介质，这些介质直接激活感觉神经元，介导皮肤瘙痒、呼吸道咳嗽/打喷嚏和支气管收缩以及胃肠道蠕动。激活后，这些外周神经元释放神经递质和神经肽，直接作用于免疫细胞以调节其功能。躯体感觉和内脏传入神经元释放包括降钙素基因相关肽、P物质和血管活性肠肽在内的神经肽，这些神经肽可作用于2型免疫细胞以驱动过敏性炎症。自主神经元释放包括乙酰胆碱和去甲肾上腺素在内的神经递质，向固有免疫细胞和适应性免疫细胞发出信号。神经免疫信号传导可能在包括特应性皮炎、哮喘和食物过敏在内的过敏性疾病的生理病理学中起核心作用。因此，更好地了解这些细胞和分子水平的神经免疫相互作用可能会带来治疗过敏性疾病的新方法。
