دورية أكاديمية
أعرض في EDS

Type 2 cytokines sensitize human sensory neurons to itch-associated stimuli.

التفاصيل البيبلوغرافية
العنوان: Type 2 cytokines sensitize human sensory neurons to itch-associated stimuli.
المؤلفون: Mack MR; Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, MA, United States., Miron Y; AnaBios, San Diego, CA, United States., Chen F; AnaBios, San Diego, CA, United States., Miller PE; AnaBios, San Diego, CA, United States., Zhang A; Medical Affairs, Sanofi, Cambridge, MA, United States., Korotzer A; Medical Affairs, Regeneron Pharmaceuticals, Tarrytown, NY, United States., Richman D; Medical Affairs, Sanofi, Cambridge, MA, United States., Bryce PJ; Immunology and Inflammation Research Therapeutic Area, Sanofi, Cambridge, MA, United States.
المصدر: Frontiers in molecular neuroscience [Front Mol Neurosci] 2023 Oct 05; Vol. 16, pp. 1258823. Date of Electronic Publication: 2023 Oct 05 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101477914 Publication Model: eCollection Cited Medium: Print ISSN: 1662-5099 (Print) Linking ISSN: 16625099 NLM ISO Abbreviation: Front Mol Neurosci Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Lausanne, Switzerland : Frontiers Research Foundation, 2008-
مستخلص: 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 ex vivo system.
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.
Competing Interests: MM, AZ, DR, and PB were employed by Sanofi during the period the study was designed and conducted. YM, FC, and PM were employed by AnaBios during the period the study was designed and conducted. AK was employed by Regeneron Pharmaceuticals during the period the study was designed and conducted.
(Copyright © 2023 Mack, Miron, Chen, Miller, Zhang, Korotzer, Richman and Bryce.)
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فهرسة مساهمة: Keywords: IL-13; IL-33; IL-4; atopic dermatitis; chronic itch; sensory neurons; type 2 cytokines
تواريخ الأحداث: Date Created: 20231023 Latest Revision: 20231030
رمز التحديث: 20231031
مُعرف محوري في PubMed: PMC10586051
DOI: 10.3389/fnmol.2023.1258823
PMID: 37868811
قاعدة البيانات: MEDLINE
الوصف
تدمد:1662-5099
DOI:10.3389/fnmol.2023.1258823