Nppb Neurons Are Sensors of Mast Cell-Induced Itch

Solinski, Hans Jürgen; Kriegbaum, Mette C.; Tseng, Pang-Yen; Earnest, Thomas; Gu, Xinglong; Barik, Arnab; Chesler, Alexander T.; Hoon, Mrinalini

doi:10.1016/j.celrep.2019.02.089

Cited by 99 publications

(119 citation statements)

References 91 publications

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“…Mast cells also release 5‐HT, LTC 4 , and sphingosine‐1 phosphate (S1P) to induce scratch responses via GRP signalling in spinal cord. Interestingly, these non‐histamine pruriception from mast cells are dependent on Nppb + ‐sensory neurons activation because 5‐HT 1F , CysLT 2 and S1P receptors were expressed in Nppb + ‐neurons (Solinski et al, ). In addition, noxious acidosis‐induced itch upon intradermal injection into mice, also activates Nppb + ‐sensory neurons via a TRPV1 channel‐dependent mechanism, and the proton‐sensing GPCR, TDAG8 (GPR65), is highly expressed on Nppb + ‐neurons (Lin et al, ; Figure ).…”

Section: Peripheral Role Of Bnp In Itchy Skinmentioning

confidence: 99%

“…Nppb TRPV1 + (Mishra & Hoon, 2013), MrgprA3 + (Usoskin et al, 2015); MrgprC11 + (Mishra & Hoon, 2013), PLCβ (Mishra & Hoon, 2013); CGRP + and IB4 + neurons ; Cysltr2 + , Htr1f + , and S1pr1 + (Solinski, Kriegbaum, et al, 2019); somatostatin (Sst) + (Huang et al, 2018); NMB + (Mishra & Hoon, 2013); Il31ra + , S100b + , Cpne6 + (…”

Section: Dorsal Horn Ventral Hornmentioning

confidence: 99%

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Interventions in the B‐type natriuretic peptide signalling pathway as a means of controlling chronic itch

Meng

Chen

Wang

2020

British J Pharmacology

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Chronic itch poses major health care and economic burdens worldwide. In 2013, B‐type natriuretic peptide (BNP) was identified as an itch‐selective neuropeptide and shown to be both necessary and sufficient to produce itch behaviour in mice. Since then, mechanistic studies of itch have increased, not only at central levels of the spinal relay of itch signalling but also in the periphery and skin. In this review, we have critically analysed recent findings from complementary pharmacological and physiological approaches, combined with genetic strategies to examine the role of BNP in itch transduction and modulation of other pruritic proteins. Additionally, potential targets and possible strategies against BNP signalling are discussed for developing novel therapeutics in itch. Overall, we aim to provide insights into drug development by altering BNP signalling to modulate disease symptoms in chronic itch, including conditions for which no approved treatment exists.

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Section: Peripheral Role Of Bnp In Itchy Skinmentioning

confidence: 99%

Section: Dorsal Horn Ventral Hornmentioning

confidence: 99%

Interventions in the B‐type natriuretic peptide signalling pathway as a means of controlling chronic itch

Meng

Chen

Wang

2020

British J Pharmacology

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“…As MrgprA3neurons include NP1 and NP3 populations (Usoskin et al, 2015), they are similarly enriched for many itch receptors and or itch-related molecules. The expression of Nppb (Natriuretic Peptide B) and Sst (somatostatin) defines the pruriceptive NP3 population that does not express MrgprA3 (Solinski et al, 2019;Usoskin et al, 2015). Cysltr2 (cysteinyl leukotriene receptor 2), Htr1f (5-Hydroxytryptamine Receptor 1F), and S1pr1 (sphingosine-1-phosphate receptor 1) are all enriched in Nppb/Sst + NP3 neurons and mediate leukotriene C4, serotonin, and sphingosine-1-phosphate-induced itch sensation, respectively (Solinski et al, 2019).…”

Section: Transcriptional Profile Of Mrgpra3 + Neuronsmentioning

confidence: 99%

“…The expression of Nppb (Natriuretic Peptide B) and Sst (somatostatin) defines the pruriceptive NP3 population that does not express MrgprA3 (Solinski et al, 2019;Usoskin et al, 2015). Cysltr2 (cysteinyl leukotriene receptor 2), Htr1f (5-Hydroxytryptamine Receptor 1F), and S1pr1 (sphingosine-1-phosphate receptor 1) are all enriched in Nppb/Sst + NP3 neurons and mediate leukotriene C4, serotonin, and sphingosine-1-phosphate-induced itch sensation, respectively (Solinski et al, 2019). Both co-receptors for IL-31 (Il31ra and osmr) are highly expressed in both MrgprA3 + and MrgprA3neurons, although MrgprA3neurons are more enriched for Il31ra, suggesting that MrgprA3 + neurons are part of the neuronal population mediating Il-31-induced itch.…”

Section: Transcriptional Profile Of Mrgpra3 + Neuronsmentioning

confidence: 99%

“…Lpar3 and Lpar5 (Lysophosphatidic acid receptor 3 and 5) are highly expressed in NP1 population as well (Liu et al, 2012;Oude Elferink et al, 2015). NP3 neurons express the most itch receptors, including two co-receptors for IL-31 (Il31ra and osmr), Cysltr2 (cysteinyl leukotriene receptor 2), Htr1f and S1pr1 (sphingosine-1-phosphate receptor 1) (Huang et al, 2018b;Mishra and Hoon, 2013;Solinski et al, 2019;Storan et al, 2015;Usoskin et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Molecular signature of pruriceptive MrgprA3⁺ neurons

Xing

Chen

Hilley

et al. 2019

Preprint

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Itch, initiated by the activation of sensory neurons, is frequently associated with dermatological or systemic diseases and significantly affects patient quality of life. MrgprA3 + sensory neurons have been identified as one of the major itch-sensing neuronal populations. Mounting evidence has demonstrated that peripheral pathological conditions induce physiological regulations of sensory neurons, which is critical for the maintenance of chronic itch sensation. However, the underlying molecular mechanisms are not clear. Here we performed RNA sequencing of genetically labeled MrgprA3 + neurons under both naï ve and allergic contact dermatitis condition.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 the main, 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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Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics

et al. 2022

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Atopic dermatitis is a chronic inflammatory skin disease. Patients with atopic dermatitis experience inflammatory lesions associated with intense itch and pain, which lead to sleep disturbance and poor mental health and quality of life. We review the molecular mechanisms underlying itch and pain symptoms in atopic dermatitis and discuss the current clinical development of treatments for moderate‐to‐severe atopic dermatitis. The molecular pathology of atopic dermatitis includes aberrant immune activation involving significant cross‐talk among the skin and immune and neuronal cells. Exogenous and endogenous triggers modulate stimulation of mediators including cytokine/chemokine expression/release by the skin and immune cells, which causes inflammation, skin barrier disruption, activation and growth of sensory neurons, itch and pain. These complex interactions among cell types are mediated primarily by cytokines, but also involve chemokines, neurotransmitters, lipids, proteases, antimicrobial peptides, agonists of ion channels or various G protein–coupled receptors. Patients with atopic dermatitis have a cytokine profile characterised by abnormal levels of interleukins 4, 12, 13, 18, 22, 31 and 33; thymic stromal lymphopoietin; and interferon gamma. Cytokine receptors mainly signal through the Janus kinase/signal transducer and activator of transcription pathway. Among emerging novel therapeutics, several Janus kinase inhibitors are being developed for topical or systemic treatment of moderate‐to‐severe atopic dermatitis because of their potential to modulate cytokine expression and release. Janus kinase inhibitors lead to changes in gene expression that have favourable effects on local and systemic cytokine release, and probably other mediators, thus successfully modulating molecular mechanisms responsible for itch and pain in atopic dermatitis.

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Nppb Neurons Are Sensors of Mast Cell-Induced Itch

Cited by 99 publications

References 91 publications

Interventions in the B‐type natriuretic peptide signalling pathway as a means of controlling chronic itch

Interventions in the B‐type natriuretic peptide signalling pathway as a means of controlling chronic itch

Molecular signature of pruriceptive MrgprA3⁺ neurons

Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics

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Nppb Neurons Are Sensors of Mast Cell-Induced Itch

Cited by 99 publications

References 91 publications

Interventions in the B‐type natriuretic peptide signalling pathway as a means of controlling chronic itch

Interventions in the B‐type natriuretic peptide signalling pathway as a means of controlling chronic itch

Molecular signature of pruriceptive MrgprA3+ neurons

Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics

Contact Info

Product

Resources

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Molecular signature of pruriceptive MrgprA3⁺ neurons