| First Author | Zhang S | Year | 2021 |
| Journal | Cell | Volume | 184 |
| Issue | 8 | Pages | 2151-2166.e16 |
| PubMed ID | 33765440 | Mgi Jnum | J:305469 |
| Mgi Id | MGI:6706325 | Doi | 10.1016/j.cell.2021.03.002 |
| Citation | Zhang S, et al. (2021) Nonpeptidergic neurons suppress mast cells via glutamate to maintain skin homeostasis. Cell 184(8):2151-2166.e16 |
| abstractText | 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. |
