美国匹兹堡大学Daniel H. Kaplan、张石群团队近日取得一项新成果。他们发现非肽能神经元通过谷氨酸抑制肥大细胞以维持皮肤稳态。这一研究成果发表在2021年3月24日出版的国际学术期刊《细胞》上。
他们发现，表达MrgprD的感觉非肽能神经元亚群的表皮神经末梢由于缺乏朗格汉斯细胞而减少。表达MrgprD的神经元的表皮神经支配或消融的丧失增加了肥大细胞基因模块（包括激活受体Mrgprb2）的表达，导致肥大细胞脱粒增加和多种疾病模型中的皮肤炎症。
表达MrgprD的神经元激动减少了模块基因的表达并抑制了肥大细胞反应。表达MrgprD的神经元释放出谷氨酸盐，该谷氨酸盐由于MrgprD激动作用而增加。抑制谷氨酸盐的释放或谷氨酸盐受体的结合产生了高反应性肥大细胞，其基因组状态类似于缺乏表达MrgprD神经元的小鼠的基因组状态。
这些数据表明，表达MrgprD的神经元通过谷氨酸释放抑制肥大细胞高反应性和皮肤炎症，从而揭示了维持皮肤免疫稳态的意外神经免疫机制。
据介绍，皮肤肥大细胞介导许多皮肤炎症过程，并与感觉传入神经元具有解剖学和功能上的联系。
附：英文原文
Title: Nonpeptidergic neurons suppress mast cells via glutamate to maintain skin homeostasis
Author: Shiqun Zhang, Tara N. Edwards, Virendra K. Chaudhri, Jianing Wu, Jonathan A. Cohen, Toshiro Hirai, Natalie Rittenhouse, Elizabeth G. Schmitz, Paul Yifan Zhou, Benjamin D. McNeil, Yi Yang, H. Richard Koerber, Tina L. Sumpter, Amanda C. Poholek, Brian M. Davis, Kathryn M. Albers, Harinder Singh, Daniel H. Kaplan
Issue&Volume: 2021-03-24
Abstract: Cutaneous mast cells mediate numerous skin inflammatory processes and have anatomicaland functional associations with sensory afferent neurons. We reveal that epidermalnerve endings from a subset of sensory nonpeptidergic neurons expressing MrgprD arereduced by the absence of Langerhans cells. Loss of epidermal innervation or ablationof MrgprD-expressing neurons increased expression of a mast cell gene module, includingthe activating receptor, Mrgprb2, resulting in increased mast cell degranulation and cutaneous inflammation in multipledisease models. Agonism of MrgprD-expressing neurons reduced expression of modulegenes and suppressed mast cell responses. MrgprD-expressing neurons released glutamatewhich was increased by MrgprD agonism. Inhibiting glutamate release or glutamate receptorbinding yielded hyperresponsive mast cells with a genomic state similar to that inmice lacking MrgprD-expressing neurons. These data demonstrate that MrgprD-expressingneurons suppress mast cell hyperresponsiveness and skin inflammation via glutamaterelease, thereby revealing an unexpected neuroimmune mechanism maintaining cutaneousimmune homeostasis.
DOI: 10.1016/j.cell.2021.03.002
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00287-7