Mendoza Alejandra, Bou-Puerto Regina, Jara Juan Sebastian, Dikiy Stanislav, Giovanelli Paolo, Correa Danilo, Manenti Susanna, Andretta Emma S, Dahia Chitra L, Rudensky Alexander Y
Howard Hughes Medical Institute and Immunology Program, Sloan Kettering Institute, and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Department of Immunology and Microbiology, Scripps Research, La Jolla, CA 92037, USA.
Sci Immunol. 2025 Sep 5;10(111):eadz6869. doi: 10.1126/sciimmunol.adz6869.
The skin integrates diverse signals discerned by sensory neurons and immune cells to elicit adaptive responses to a range of stresses. Considering interactions between nervous and immune systems, we examined whether regulatory T (T) cells, which suppress systemic and local inflammation, can modulate activation of peripheral neurons. Acute T cell "loss of function" increased neuronal activation to noxious stimuli independently of their immunosuppressive function. This activity was mediated by a T cell subset capable of production of enkephalins encoded by the gene , whose expression is facilitated by combined TCR and glucocorticoid receptor signaling. Punctual selective depletion of -expressing T cells or specific ablation of in T cells increased neuronal activation in response to noxious stimuli and associated inflammation. Our study indicates that a population of tissular T cells exhibits neuromodulatory activity to restrain local inflammation in the skin.
皮肤整合由感觉神经元和免疫细胞识别的多种信号，以引发对一系列应激的适应性反应。考虑到神经系统和免疫系统之间的相互作用，我们研究了抑制全身和局部炎症的调节性T（Treg）细胞是否能调节外周神经元的激活。急性T细胞“功能丧失”增加了神经元对有害刺激的激活，这与其免疫抑制功能无关。这种活性由一个能够产生由该基因编码的脑啡肽的T细胞亚群介导，其表达通过TCR和糖皮质激素受体信号的联合作用而促进。表达该基因的T细胞的点状选择性耗竭或T细胞中该基因的特异性缺失增加了对有害刺激和相关炎症的神经元激活。我们的研究表明，一群组织性T细胞表现出神经调节活性以抑制皮肤中的局部炎症。
