A mast cell–thermoregulatory neuron circuit axis regulates hypothermia in anaphylaxis DOI
Chunjing Bao, Chen Ouyang, Huaxin Sheng

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(81)

Published: March 17, 2023

IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis triggered when blood-borne allergens activate IgE-bound perivascular mast cells (MCs) throughout the body, causing extensive release of MC mediators. Through precipitating vasodilatation vascular leakage, these mediators are believed trigger a sharp drop in blood pressure humans core body temperature animals. We report that IgE/MC-mediated mice associated with also requires body’s thermoregulatory neural circuit. This circuit activated granule-borne chymase from MCs deposited on proximal TRPV1 + sensory neurons stimulates them via protease-activated receptor-1. triggers activation network, which rapidly attenuates brown adipose tissue thermogenesis cause hypothermia. Mice deficient either or exhibited limited anaphylaxis, and, wild-type mice, could be recapitulated simply by systemically activating neurons. Thus, addition their well-known effects vasculature, products, especially chymase, promote

Language: Английский

Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury DOI Creative Commons
William Renthal, Ivan Tochitsky,

Lite Yang

et al.

Neuron, Journal Year: 2020, Volume and Issue: 108(1), P. 128 - 144.e9

Published: Aug. 17, 2020

Language: Английский

Citations

411
The emergence of transcriptional identity in somatosensory neurons DOI
Nikhil Sharma,

Kali Flaherty,

Karina Lezgiyeva

et al.

Nature, Journal Year: 2020, Volume and Issue: 577(7790), P. 392 - 398

Published: Jan. 8, 2020

Language: Английский

Citations

397
Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors DOI Open Access
Diana Tavares‐Ferreira, Stephanie Shiers, Pradipta Ray

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(632)

Published: Feb. 16, 2022

Nociceptors are specialized sensory neurons that detect damaging or potentially stimuli and found in the dorsal root ganglia (DRG) trigeminal ganglia. These critical for generation of neuronal signals ultimately create perception pain. also primary targets treating acute chronic Single-cell transcriptomics on mouse nociceptors has transformed our understanding pain mechanisms. We sought to generate equivalent information human with goal identifying transcriptomic signatures nociceptors, species differences potential drug targets. used spatial molecularly characterize transcriptomes single DRG from eight organ donors. identified 12 clusters neurons, 5 which C as well 1 low-threshold mechanoreceptors (LTMRs), Aβ nociceptor, 2 Aδ, Aβ, proprioceptor subtypes. By focusing expression profiles ion channels, G protein-coupled receptors (GPCRs), other pharmacological targets, we provided a rich map direct comparison neuron transcriptomes. compared subtypes nonhuman primates showing conserved patterns gene among many cell types but divergence specific nociceptor subsets. Last, sex subpopulation transcriptomes, including marked increase calcitonin-related polypeptide alpha (CALCA) female pruritogen receptor-enriched nociceptors. This comprehensive characterization might open door development better treatments disorders.

Language: Английский

Citations

286
The mechanosensory neurons of touch and their mechanisms of activation DOI
Annie Handler, David D. Ginty

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(9), P. 521 - 537

Published: July 26, 2021

Language: Английский

Citations

273
Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models DOI Creative Commons
Lauren L. Orefice,

Jacqueline R. Mosko,

Danielle T. Morency

et al.

Cell, Journal Year: 2019, Volume and Issue: 178(4), P. 867 - 886.e24

Published: Aug. 1, 2019

Language: Английский

Citations

207
STING controls nociception via type I interferon signalling in sensory neurons DOI
Christopher R. Donnelly, Changyu Jiang, Amanda S. Andriessen

et al.

Nature, Journal Year: 2021, Volume and Issue: 591(7849), P. 275 - 280

Published: Jan. 13, 2021

Language: Английский

Citations

170
Ion Channel Degeneracy, Variability, and Covariation in Neuron and Circuit Resilience DOI Open Access
Jean‐Marc Goaillard, Eve Marder

Annual Review of Neuroscience, Journal Year: 2021, Volume and Issue: 44(1), P. 335 - 357

Published: March 26, 2021

The large number of ion channels found in all nervous systems poses fundamental questions concerning how the characteristic intrinsic properties single neurons are determined by specific subsets they express. All display many different with overlapping voltage- and time-dependent properties. We speculate that these promote resilience neuronal function. Individual same cell type show variability channel conductance densities even though can generate reliable similar behavior. This complicates a simple assignment function to any is associated variable responses perturbations, deletions, pharmacological manipulation. Ion genes often strong positively correlated expression, which may result from molecular developmental rules determine expressed given type.

Language: Английский

Citations

158
IL-23/IL-17A/TRPV1 axis produces mechanical pain via macrophage-sensory neuron crosstalk in female mice DOI Creative Commons
Xin Luo, Chen Ouyang, Zilong Wang

et al.

Neuron, Journal Year: 2021, Volume and Issue: 109(17), P. 2691 - 2706.e5

Published: July 19, 2021

Although sex dimorphism is increasingly recognized as an important factor in pain, female-specific pain signaling not well studied. Here we report that administration of IL-23 produces mechanical (mechanical allodynia) female but male mice, and chemotherapy-induced selectively impaired mice lacking Il23 or Il23r. IL-23-induced promoted by estrogen suppressed androgen, suggesting involvement hormones. requires C-fiber nociceptors TRPV1 to produce does directly activate nociceptor neurons. Notably, IL-17A release from macrophages evoke females. Low-dose activates induces only Finally, deletion receptor subunit α (ERα) TRPV1+ abolishes IL-23- IL-17-induced These findings demonstrate the IL-23/IL-17A/TRPV1 axis regulates via neuro-immune interactions. Our study also reveals at both immune neuronal levels.

Language: Английский

Citations

142
Human and mouse trigeminal ganglia cell atlas implicates multiple cell types in migraine DOI Creative Commons

Lite Yang,

Mengyi Xu, Shamsuddin A. Bhuiyan

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(11), P. 1806 - 1821.e8

Published: March 28, 2022

Language: Английский

Citations

110
PIEZO1 transduces mechanical itch in mice DOI Creative Commons
Rose Z. Hill,

Meaghan Loud,

Adrienne E. Dubin

et al.

Nature, Journal Year: 2022, Volume and Issue: 607(7917), P. 104 - 110

Published: June 22, 2022

Itch triggers scratching, a behavioural defence mechanism that aids in the removal of harmful irritants and parasites1. Chemical itch is triggered by many endogenous exogenous cues, such as pro-inflammatory histamine, which released during an allergic reaction1. Mechanical can be light sensations wool fibres or crawling insect2. In contrast to chemical pathways, have been extensively studied, mechanisms underlie transduction mechanical are largely unknown. Here we show mechanically activated ion channel PIEZO1 (ref. 3) selectively expressed itch-specific sensory neurons required for their currents. Loss function peripheral greatly reduces evoked scratching behaviours both acute chronic itch-evoked sensitization. Finally, mice expressing gain-of-function Piezo1 allele4 exhibit enhanced behaviours. Our studies reveal polymodal nature identify role sensation itch.

Language: Английский

Citations

105