Francelin Carolina, Veneziani Luciana Peixoto, Farias Alessandro Dos Santos, Mendes-da-Cruz Daniella Arêas, Savino Wilson
Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Front Cell Dev Biol. 2021 Apr 13;9:668067. doi: 10.3389/fcell.2021.668067. eCollection 2021.
The existence of a crosstalk between the nervous and immune systems is well established. Neurotransmitters can be produced by immune cells, whereas cytokines can be secreted by cells of nervous tissues. Additionally, cells of both systems express the corresponding receptors. Herein, we discuss the thymus as a paradigm for studies on the neuroimmune network. The thymus is a primary lymphoid organ responsible for the maturation of T lymphocytes. Intrathymic T-cell development is mostly controlled by the thymic microenvironment, formed by thymic epithelial cells (TEC), dendritic cells, macrophages, and fibroblasts. Developing thymocytes and microenvironmental cells can be influenced by exogenous and endogenous stimuli; neurotransmitters are among the endogenous molecules. Norepinephrine is secreted at nerve endings in the thymus, but are also produced by thymic cells, being involved in controlling thymocyte death. Thymocytes and TEC express acetylcholine receptors, but the cognate neurotransmitter seems to be produced and released by lymphoid and microenvironmental cells, not by nerve endings. Evidence indicates that, among others, TECs also produce serotonin and dopamine, as well as somatostatin, substance P, vasoactive intestinal peptide (VIP) and the typical pituitary neurohormones, oxytocin and arg-vasopressin. Although functional data of these molecules in the thymus are scarce, they are likely involved in intrathymic T cell development, as exemplified by somatostatin, which inhibits thymocyte proliferation, differentiation, migration and cytokine production. Overall, intrathymic neuroimmune interactions include various neurotransmitters, most of them of non-neuronal origin, and that should be placed as further physiological players in the general process of T-cell development.
神经和免疫系统之间存在相互作用，这一点已得到充分证实。免疫细胞可产生神经递质，而神经组织细胞可分泌细胞因子。此外，这两个系统的细胞都表达相应的受体。在此，我们将胸腺作为神经免疫网络研究的一个范例进行讨论。胸腺是一个主要的淋巴器官，负责T淋巴细胞的成熟。胸腺内T细胞的发育主要受胸腺微环境的控制，胸腺微环境由胸腺上皮细胞（TEC）、树突状细胞、巨噬细胞和成纤维细胞组成。发育中的胸腺细胞和微环境细胞可受到外源性和内源性刺激的影响；神经递质是内源性分子之一。去甲肾上腺素在胸腺的神经末梢分泌，但也由胸腺细胞产生，参与控制胸腺细胞死亡。胸腺细胞和TEC表达乙酰胆碱受体，但相关神经递质似乎是由淋巴细胞和微环境细胞产生和释放的，而非神经末梢。有证据表明，除其他外，TEC还产生5-羟色胺和多巴胺，以及生长抑素、P物质、血管活性肠肽（VIP）和典型的垂体神经激素、催产素和精氨酸加压素。尽管这些分子在胸腺中的功能数据很少，但它们可能参与胸腺内T细胞的发育，以生长抑素为例，它可抑制胸腺细胞的增殖分化、迁移和细胞因子的产生。总体而言，胸腺内的神经免疫相互作用包括多种神经递质，其中大多数并非来源于神经元，它们应被视为T细胞发育一般过程中的其他生理参与者。
