ArticleFrontiers in molecular neuroscience2023
Type 2 cytokines sensitize human sensory neurons to itch-associated stimuli.
Article in Frontiers in molecular neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Integrated Clinical Trial and Molecular Profiling Reveals Immune Drivers of Chronic Hand Eczema.Allergy · 2026Trial
- Efficacy and Safety of Dupilumab in Adults with Prurigo Nodularis with or Without Atopic Comorbidities: A Subgroup Analysis from Two Randomized Phase III Clinical Trials.American journal of clinical dermatology · 2026Trial
- Shared Mechanistic Pathways in Bullous Pemphigoid, Chronic Spontaneous Urticaria, Prurigo Nodularis, and Chronic Prurigo of Unknown Origin: Implications for Targeted Therapies.American journal of clinical dermatology · 2026Review
- Topical MongolianJournal of clinical biochemistry and nutrition · 2026Article
- Review
- Cross-Talk between Neurons and Immune Cells in Pruritus: from Mechanisms To Medicines.Current allergy and asthma reports · 2026Review
- The Role of Neuro-Immune Regulation in the Pathogenesis of Psoriasis.Journal of immunology research · 2026Review
- Modulatory effects of bioactive natural compounds on pruritic pathways: mechanistic basis and therapeutic prospects.Inflammopharmacology · 2025Review
- Host-Microbiome Interactions in Chronic Itch.Journal of clinical medicine · 2025Review
- Transcriptomic profiling of dorsal root ganglia in atopic and healthy dogs: A comparative RNA sequencing study with implications in cutaneous itch research.Veterinary dermatology · 2025Article
- Comparative Efficacy and Safety of Tralokinumab and Dupilumab in Moderate-to-Severe Atopic Dermatitis: A Narrative Review.Journal of clinical medicine · 2025Review
- Prevalence and Mechanisms of Itch in Chronic Wounds: A Narrative Review.Journal of clinical medicine · 2025Review
- Practical guide for the diagnosis and treatment of localized and generalized cutaneous pruritus (chronic itch with no underlying pruritic dermatosis).The Journal of dermatology · 2025Review
- Mast cell-neuron axis as a core mechanism in chronic pruritus of atopic dermatitis: from mechanistic insights to therapeutic targets.Frontiers in immunology · 2025Review
- Immunomodulatory and anti-inflammatory effects of agave fructans in atopic dermatitis: gut microbiota and short-chain fatty acid implication.Frontiers in immunology · 2025Article
- Atopic dermatitis and food allergy: More than sensitization.Mucosal immunology · 2024Review
- Dupilumab improves pruritus and skin lesions in patients with prurigo nodularis: Pooled results from 2 phase 3 trials (LIBERTY-PN PRIME and PRIME2).JAAD international · 2024Article
- Sensory sentinels: Neuroimmune detection and food allergy.Immunological reviews · 2024Review
- Interleukin Profiling in Atopic Dermatitis and Chronic Nodular Prurigo.International journal of molecular sciences · 2024Article
- How underappreciated autoinflammatory (innate immunity) mechanisms dominate disparate autoimmune disorders.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Chronic itch is a central symptom of atopic dermatitis. Cutaneous afferent neurons express receptors interleukins (IL)-4, IL-13, and IL-33, which are type 2 cytokines that are elevated in atopic dermatitis. These neuronal cytokine receptors were found to be required in several murine models of itch. Prior exposure of neurons to either IL-4 or IL-33 increased their response to subsequent chemical pruritogens in mice but has not been previously examined in humans. The objective of the present study was to determine if type 2 cytokine stimulation sensitizes sensory neurons to future itch stimuli in a fully human Methods: We measured calcium flux from human dorsal root ganglia cultures from cadaveric donors in response to pruritogens following transient exposure to type 2 cytokines. We also measured their effect on neuronal calcium flux and changes in gene expression by RNA sequencing. Results: Type 2 cytokines (IL-4, IL-13, and IL-33) were capable of sensitizing human dorsal root ganglia neurons to both histaminergic and nonhistaminergic itch stimuli. Sensitization was observed after only 2 h of pruritogen incubation. We observed rapid neuronal calcium flux in a small subset of neurons directly in response to IL-4 and to IL-13, which was dependent on the presence of extracellular calcium. IL-4 and IL-13 induced a common signature of upregulated genes after 24 h of exposure that was unique from IL-33 and non-type 2 inflammatory stimuli. Discussion: This study provides evidence of peripheral neuron sensitization by type 2 cytokines as well as broad transcriptomic effects in human sensory ganglia. These studies identify both unique and overlapping roles of these cytokines in sensory neurons.
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Registered trials
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.