Nonpeptidergic neurons suppress mast cells via glutamate to maintain skin homeostasis
| Autor: | Amanda C. Poholek, Natalie Rittenhouse, Tara N. Edwards, Tina L. Sumpter, Jianing Wu, Brian M. Davis, Shiqun Zhang, Virendra K. Chaudhri, Kathryn M. Albers, Paul Yifan Zhou, Harinder Singh, Yi Yang, Daniel H. Kaplan, Elizabeth G. Schmitz, Jonathan A. Cohen, Toshiro Hirai, Benjamin D. McNeil, H. Richard Koerber |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Langerhans cell
Integrin beta Chains Glutamic Acid Kainate receptor Inflammation Dermatitis Biology General Biochemistry Genetics and Molecular Biology Receptors G-Protein-Coupled Glutamate receptor binding 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Diphtheria Toxin Mast Cells Cells Cultured 030304 developmental biology Skin Mice Knockout Neurons 0303 health sciences Degranulation Glutamate receptor Mast cell Cell biology Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Langerhans Cells beta-Alanine Female medicine.symptom Free nerve ending 030217 neurology & neurosurgery |
| Zdroj: | Cell. 184(8) |
| ISSN: | 1097-4172 |
| Popis: | Cutaneous mast cells mediate numerous skin inflammatory processes and have anatomical and functional associations with sensory afferent neurons. We reveal that epidermal nerve endings from a subset of sensory nonpeptidergic neurons expressing MrgprD are reduced by the absence of Langerhans cells. Loss of epidermal innervation or ablation of MrgprD-expressing neurons increased expression of a mast cell gene module, including the activating receptor, Mrgprb2, resulting in increased mast cell degranulation and cutaneous inflammation in multiple disease models. Agonism of MrgprD-expressing neurons reduced expression of module genes and suppressed mast cell responses. MrgprD-expressing neurons released glutamate which was increased by MrgprD agonism. Inhibiting glutamate release or glutamate receptor binding yielded hyperresponsive mast cells with a genomic state similar to that in mice lacking MrgprD-expressing neurons. These data demonstrate that MrgprD-expressing neurons suppress mast cell hyperresponsiveness and skin inflammation via glutamate release, thereby revealing an unexpected neuroimmune mechanism maintaining cutaneous immune homeostasis. |
| Databáze: | OpenAIRE |
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