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Nppb Neurons Are Sensors Of Mast Cell-Induced Itch

ABSTRACT: Itch is an unpleasant skin sensation which can be triggered by exposure to many chemicals including those released by mast cells. The Nppb-expressing class of sensory neurons when activated elicit scratching responses in mice, however, it is unclear which itch-inducing agents stimulate these cells and the receptors involved. Here, we identify receptors expressed by Nppb-neurons and demonstrate the functional importance of these receptors as sensors of endogenous pruritogens released by mast cells. Our search for receptors in Nppb-neurons revealed that they express leukotriene, serotonin, and sphingosine-1-phosphate receptors. Targeted cell ablation, calcium imaging of primary sensory neurons, and conditional receptor knockout studies demonstrate that these receptors induce itch by the direct stimulation of Nppb-neurons and neurotransmission through the canonical GRP-dependent spinal cord itch pathway. Together our results define a molecular and cellular pathway for mast cell-induced itch.

ORGANISM(S): Mus musculus

PROVIDER: GSE125626 | GEO | 2019/03/26

REPOSITORIES: GEO

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Nppb Neurons Are Sensors Of Mast Cell-Induced Itch

Project description:Nppb Neurons Are Sensors Of Mast Cell-Induced Itch

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Molecular signature of pruriceptive MrgprA3+ neurons

Project description:We performed RNA sequencing of genetically labeled MrgprA3+ neurons under both naïve and allergic contact dermatitis conditions. Our results revealed the unique molecular signature of itch-sensing neurons and the distinct transcriptional profile changes that result in response to dermatitis. We found enrichment of nine Mrgpr family members and two histamine receptors in MrgprA3+ neurons, suggesting that MrgprA3+ neurons are a direct neuronal target for histamine and Mrgprs agonists. In addition, Ptpn6 and Pcdh12 were identified as novel and highly selective markers of MrgprA3+ neurons. We also discovered that MrgprA3+ neurons respond to skin dermatitis in a way that is unique from other sensory neurons by regulating a combination of transcriptional factors, ion channels, and key molecules involved in synaptic transmission. These results significantly increase our knowledge of itch transmission and uncover potentially novel targets for combating itch.

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IL-33-activated calcitonin gene-related peptide-producing memory Th2 cells co-operate with somatosensory neurons to induce conjunctival itch

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Transcriptional regulation of human dorsal root ganglia cultures by type 2 cytokines

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