Evidence map›Paper›PMID 24373353›Full record

ArticleThe Journal of allergy and clinical immunology2014

A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: Involvement of TRPV1 and TRPA1.

Ferda Cevikbas, Xidao Wang, Tasuku Akiyama, Cordula Kempkes, Terhi Savinko, Attila Antal, Gabriela Kukova, Timo Buhl, Akihiko Ikoma, Joerg Buddenkotte and 8 more

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In one paragraph

Article in The Journal of allergy and clinical immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 352 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
352citing papers in PubMed, 3 pooled it
33.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

352 citing papers in PubMed, 3 syntheses or guidelines pooled it, 746 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Rapid improvement of itch with nemolizumab in atopic dermatitis and prurigo nodularis phase 3 studies.Journal of the European Academy of Dermatology and Venereology : JEADV · 2026
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  19. Immunopathogenesis of itch: an integrative framework for chronic pruritus.JID innovations : skin science from molecules to population health · 2026
    Review
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292 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 4 countries.

Ferda CevikbasDepartments of Dermatology and Surgery, University of California, San Francisco, San Francisco, Calif; Department of Dermatology, University Hospital Düsseldorf, Düsseldorf, Germany.
Xidao WangDepartment of Anatomy and the W.M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, Calif.
Tasuku AkiyamaDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Calif.
Cordula KempkesDepartments of Dermatology and Surgery, University of California, San Francisco, San Francisco, Calif.
Terhi SavinkoUnit of Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
Attila AntalDepartment of Dermatology, University Hospital Düsseldorf, Düsseldorf, Germany.
Gabriela KukovaDepartment of Dermatology, University Hospital Düsseldorf, Düsseldorf, Germany.
Timo BuhlDepartments of Dermatology and Surgery, University of California, San Francisco, San Francisco, Calif.
Akihiko IkomaDepartments of Dermatology and Surgery, University of California, San Francisco, San Francisco, Calif.
Joerg BuddenkotteDepartment of Dermatology, University Hospital Münster, Muenster, Germany.
Vassili SoumelisDepartment of Immunology, Institut Curie, Paris, France.
Micha FeldDepartment of Dermatology, University Hospital Düsseldorf, Düsseldorf, Germany.
Harri AleniusUnit of Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
Stacey R DillonZymoGenetics (a Bristol-Myers Squibb Company), Seattle, Wash.
Earl CarstensDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Calif.
Bernhard HomeyDepartment of Dermatology, University Hospital Düsseldorf, Düsseldorf, Germany. Electronic address: bernhard.homey@uni-duesseldorf.de.
Allan BasbaumDepartment of Anatomy and the W.M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, Calif. Electronic address: Allan.Basbaum@ucsf.edu.
Martin SteinhoffDepartments of Dermatology and Surgery, University of California, San Francisco, San Francisco, Calif; Department of Dermatology, University Hospital Düsseldorf, Düsseldorf, Germany. Electronic address: SteinhoffM@derm.ucsf.edu.
University of California, San Francisco · USDüsseldorf University Hospital · DEFinnish Institute of Occupational Health · FIUniversity of California, Davis · USBristol-Myers Squibb (Germany) · DEHeinrich Heine University Düsseldorf · DEInstitut Curie · FRUniversity Hospital Münster · DE

Funding

BRAINSTEM CONTROL OF PAIN TRANSMISSIONR01NS014627 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASBAUM, ALLAN I. · 1985 to 2016
$3.9M
Brainstem control of pain transmissionR37NS014627 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASBAUM, ALLAN I. · 2008 to 2014
$3.6M
Spinal mechanisms of itchR01AR057194 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CARSTENS, EARL E · 2009 to 2019
$3.4M
Cytokine Signaling in Neurons: Inflammation, Pain and PruritisR01AR059402 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEINHOFF, MARTIN · 2011 to 2013
$1.0M
Warmth enhancement of itch via TRPV4R00AR063228 · NIAMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI AKIYAMA, TASUKU · 2014 to 2016
$705k
Warmth enhancement of itch via TRPV4K99AR063228 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI AKIYAMA, TASUKU · 2013 to 2014
$176k
NIAMS NIH HHS AR057194NIAMS NIH HHS AR059402NIAMS NIH HHS K99 AR063228NIAMS NIH HHS R00 AR063228NIAMS NIH HHS R01 AR057194NIAMS NIH HHS R01 AR059402NINDS NIH HHS NS14627NINDS NIH HHS R01 NS014627NINDS NIH HHS R37 NS014627
6 · The paper itself

Abstract

backgroundAlthough the cytokine IL-31 has been implicated in inflammatory and lymphoma-associated itch, the cellular basis for its pruritic action is yet unclear.

objectiveWe sought to determine whether immune cell-derived IL-31 directly stimulates sensory neurons and to identify the molecular basis of IL-31-induced itch.

methodsWe used immunohistochemistry and quantitative real-time PCR to determine IL-31 expression levels in mice and human subjects. Immunohistochemistry, immunofluorescence, quantitative real-time PCR, in vivo pharmacology, Western blotting, single-cell calcium imaging, and electrophysiology were used to examine the distribution, functionality, and cellular basis of the neuronal IL-31 receptor α in mice and human subjects.

resultsAmong all immune and resident skin cells examined, IL-31 was predominantly produced by TH2 and, to a significantly lesser extent, mature dendritic cells. Cutaneous and intrathecal injections of IL-31 evoked intense itch, and its concentrations increased significantly in murine atopy-like dermatitis skin. Both human and mouse dorsal root ganglia neurons express IL-31RA, largely in neurons that coexpress transient receptor potential cation channel vanilloid subtype 1 (TRPV1). IL-31-induced itch was significantly reduced in TRPV1-deficient and transient receptor channel potential cation channel ankyrin subtype 1 (TRPA1)-deficient mice but not in c-kit or proteinase-activated receptor 2 mice. In cultured primary sensory neurons IL-31 triggered Ca(2+) release and extracellular signal-regulated kinase 1/2 phosphorylation, inhibition of which blocked IL-31 signaling in vitro and reduced IL-31-induced scratching in vivo.

conclusionIL-31RA is a functional receptor expressed by a small subpopulation of IL-31RA(+)/TRPV1(+)/TRPA1(+) neurons and is a critical neuroimmune link between TH2 cells and sensory nerves for the generation of T cell-mediated itch. Thus targeting neuronal IL-31RA might be effective in the management of TH2-mediated itch, including atopic dermatitis and cutaneous T-cell lymphoma.

Indexed as

AnimalsCalcium ChannelsCells, CulturedFemaleGanglia, SpinalHumansInterleukinsMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsPruritusReceptors, InterleukinSensory Receptor CellsSkinTh2 CellsCalcium ChannelsIL31 protein, humanIL31RA protein, humanIl31ra protein, mouseinterleukin-31, mouseInterleukinsNerve Tissue ProteinsReceptors, InterleukinTransient Receptor Potential ChannelsTRPA1 Cation ChannelTRPA1 protein, humanTrpa1 protein, mouseTRPV1 protein, humanTRPV1 protein, mouseTRPV Cation ChannelsADAITCAllyl isothiocyanateatopic dermatitisAtopic dermatitisCytokineDorsal root gangliaDRGERKExtracellular signal-regulated kinaseGastrin-releasing peptide receptorGRPRHanks balanced salt solutionHBSSHigh-power fieldhpfIB4Isolectin B4KnockoutKOMas-related G protein–coupled receptorMEKMitogen-activated protein kinase enzymeMrgprNatriuretic peptide receptor ANPR-AOncostatin M receptor βOSMRβOVAOvalbuminPAR-2Proteinase-activated receptor 2qPCRQuantitative real-time PCRSCSEBsensory nerveskinSpinal cordStaphylococcal enterotoxin BTGTransient receptor channel potential cation channel ankyrin subtype 1Transient receptor potential cation channel vanilloid subtype 1transient receptor potential channelTrigeminal ganglionTRPA1TRPV1

Identifiers

PMID24373353
PMCPMC3960328
OpenAlexW2147889176

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.