Type 2 cytokines pleiotropically modulate sensory nerve architecture and neuroimmune interactions to mediate itch [Mouse ear pinnae]
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ABSTRACT:
PROVIDER: PRJNA1261039 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33486434_1.fastq.gz | Fastqsanger.gz | |||
| SRR33486434_2.fastq.gz | Fastqsanger.gz | |||
| SRR33486435_1.fastq.gz | Fastqsanger.gz | |||
| SRR33486435_2.fastq.gz | Fastqsanger.gz | |||
| SRR33486436_1.fastq.gz | Fastqsanger.gz |
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Project description:Background: Anti-type 2 cytokine therapies represent promising interventions for chronic itch; however, their precise mechanisms in restoring nerve architecture and mitigating inflammation and pruritus remain incompletely understood. This study aimed to elucidate the mechanistic roles of IL-4, IL-13, and IL-31 in the pathophysiology of itch associated with type 2 inflammatory skin diseases. Methods: The effect of IL-4, IL-13, and/or IL-31 on neurite outgrowth and/or transcriptomic changes were analyzed in human and mouse dorsal root ganglion (DRG) neuronal cultures. Mouse ear pinnae were processed for histologic, transcriptomic, and proteomic analyses 4 days after intradermal injection of IL-4, IL-13, and/or IL-31. To evaluate functional correlations with neuronal responses, mice were subcutaneously challenged with IL-4, IL-13, and/or IL-31, and scratching behavior was monitored. Association between IL-4/IL-13–IL-4Rα axis and severity of atopic dermatitis (AD) was evaluated through correlative analyses of human DRG transcriptomic changes and AD transcriptomic datasets (GSE130588 and BioMap consortium). Results: IL-4 and IL-13 promote mouse and human DRG sensory neuron growth, with effects similar to or greater than IL-31. In mice, intradermal IL-4, IL-13, and IL-31 increased epidermal nerve growth; however, only IL-4 and IL-13 induced hyperplasia and immune cell recruitment. Multi-omic analyses revealed that IL-4 and IL-13 have a broader impact on neuroimmune interactions than IL-31. In a murine DRG neuron-eosinophil co-culture, IL-4Rα blockade reduced neurite growth. IL-13 and IL-31 elicited acute scratching, demonstrating their roles as direct pruritogens; IL-4 synergistically enhanced IL-13-induced itch, resulting in greater pruritic responses than IL-31. Additionally, a set of itch-associated genes upregulated by IL-4 and IL-13 and downregulated by dupilumab-mediated IL-4Rα blockade in human DRG neuronal cultures showed positive correlation with AD severity. Conclusions: These findings establish the IL-4/IL-13–IL-4Rα axis as a key regulator of inflammatory skin nerve innervation, neuroimmune interactions, barrier integrity, and itch response, highlighting its mechanistic role in modulating sensory neuronal function and shaping the inflammatory microenvironment that drives itch pathophysiology.
2025-05-15 | GSE296778 | GEO
Project description:Background: Anti-type 2 cytokine therapies represent promising interventions for chronic itch; however, their precise mechanisms in restoring nerve architecture and mitigating inflammation and pruritus remain incompletely understood. This study aimed to elucidate the mechanistic roles of IL-4, IL-13, and IL-31 in the pathophysiology of itch associated with type 2 inflammatory skin diseases. Methods: The effect of IL-4, IL-13, and/or IL-31 on neurite outgrowth and/or transcriptomic changes were analyzed in human and mouse dorsal root ganglion (DRG) neuronal cultures. Mouse ear pinnae were processed for histologic, transcriptomic, and proteomic analyses 4 days after intradermal injection of IL-4, IL-13, and/or IL-31. To evaluate functional correlations with neuronal responses, mice were subcutaneously challenged with IL-4, IL-13, and/or IL-31, and scratching behavior was monitored. Association between IL-4/IL-13–IL-4Rα axis and severity of atopic dermatitis (AD) was evaluated through correlative analyses of human DRG transcriptomic changes and AD transcriptomic datasets (GSE130588 and BioMap consortium). Results: IL-4 and IL-13 promote mouse and human DRG sensory neuron growth, with effects similar to or greater than IL-31. In mice, intradermal IL-4, IL-13, and IL-31 increased epidermal nerve growth; however, only IL-4 and IL-13 induced hyperplasia and immune cell recruitment. Multi-omic analyses revealed that IL-4 and IL-13 have a broader impact on neuroimmune interactions than IL-31. In a murine DRG neuron-eosinophil co-culture, IL-4Rα blockade reduced neurite growth. IL-13 and IL-31 elicited acute scratching, demonstrating their roles as direct pruritogens; IL-4 synergistically enhanced IL-13-induced itch, resulting in greater pruritic responses than IL-31. Additionally, a set of itch-associated genes upregulated by IL-4 and IL-13 and downregulated by dupilumab-mediated IL-4Rα blockade in human DRG neuronal cultures showed positive correlation with AD severity. Conclusions: These findings establish the IL-4/IL-13–IL-4Rα axis as a key regulator of inflammatory skin nerve innervation, neuroimmune interactions, barrier integrity, and itch response, highlighting its mechanistic role in modulating sensory neuronal function and shaping the inflammatory microenvironment that drives itch pathophysiology.
2025-05-15 | GSE296776 | GEO
Project description:Type 2 cytokines pleiotropically modulate sensory nerve architecture and neuroimmune interactions to mediate itch [Human DRG]
| PRJNA1261045 | ENA
Project description:The aim of this study was to establish an intradermal ear injection model to evaluate the effects of IL-36γ and IL-17A in psoriasis.The cytokines IL-36γ and IL-17A were injected intradermally alone or in combination into the ear pinnae of C57BL/6 mice. Ear thickness measurement was performed daily. After 4 days mice were euthanized and a gene expression profiling was conducted.
2021-09-01 | GSE175732 | GEO
Project description:Mammals have evolved neurophysiologic reflexes such as coughing and scratching to expel invading pathogens and noxious environmental factors. It is well established that these responses are also associated with chronic inflammatory diseases such as asthma and atopic dermatitis. However, the mechanisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Here, we show that the type 2 cytokines IL-4 and IL-13 directly stimulate sensory neurons and that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling. In proof-of-concept clinical studies, we further show that patients with recalcitrant chronic itch markedly improve when treated with JAK inhibitors. Thus, signaling mechanisms previously ascribed to the immune system may represent novel therapeutic targets within the nervous system. Collectively, these studies reveal an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior.
2017-09-18 | GSE90883 | GEO
Project description:The nervous system coordinates with the immune system to detect and respond to harmful stimuli. Inflammation is a universal response to injury and infection that involves the release of cytokines. While it is known that information about cytokines is transmitted from the body to the brain, how the nervous system encodes specific cytokines in the form of neural activity is not well understood. Using in vivo calcium imaging, we show that vagal sensory neurons within the nodose ganglia exhibit distinct real-time neuronal responses to inflammatory cytokines. Some neurons respond selectively to individual cytokines, while others encode multiple cytokines with distinct activity patterns. In a mouse model of colitis, inflammation increased the baseline activity of these neurons but decreased responsiveness to specific cytokines, reflecting altered neural excitability. Transcriptomic analysis of vagal ganglia from colitis mice revealed downregulation of cytokine signaling pathways, while neuronal activity pathways were upregulated. Thus, nodose ganglia neurons perform real-time encoding of cytokines at the first neural station in a body-brain axis, providing a new framework for studying the dynamic nature of neuroimmune communication.
2025-04-16 | GSE294447 | GEO
Project description:There is not information regards the role of miRNAs in the development of the external ear in mammals. The aim of this study was to determine the stage-specific expression of miRNAs during external ear development in order to identify miRNAs and their possible targets. GeneChip miRNA 3.0 arrays by Affymetrix were used to obtain miRNA expression profiles from mice fetal pinnae and skin back tissues at 13.5 dpc and 14.5 dpc, biological triplicates for each tissue were analyzed; one litter represents one biological replica, each litter with 16 fetuses in average.
2015-12-31 | E-GEOD-64945 | biostudies-arrayexpress
Project description:The dorsal root ganglion (DRG) neurons take in charge of primary detection and transmission of peripheral pain and itch stimuli, however, as two distinct noxious sensation, it is still attractive for this field that how the DRG neurons differentially response and code pain and itch. Here, we investigate the response and activation spectrum of DRG neurons under peripheral pain and itch stimuli using in vivo two-photon calcium imaging, and find differences in the responsive intensity to pain and itch between multisensory neurons (both pain and itch) and single-sensory neurons (either pain or itch). Besides, single-cell RNA sequencing (scRNA-seq) is used to reveal the heterogeneity of distinct subpopulations based on their expression of pain- or itch-related marker genes and indicates the similarity and difference of their transcriptomic changes under chronic pain and itch. Our results will provide fundamental insights to the peripheral pain and itch differential coding mechanism, moreover, benefit the development of pain and itch therapies.
2024-11-20 | GSE271186 | GEO
Project description:In order to study the effect of UII on the transcription level regulation of itch-related genes in sensory neurons and keratinocytes, and to apply UII in mouse dorsal root ganglion neuronal cells and keratinocytes, the study showed that UII significantly upregulated the expression of various characteristics of atopic dermatitis and itch-related genes, such as Fasl, Mrgprx1, Amy2a3, INHBA, IL36G, STEAP2, etc.
2025-11-23 | GSE218749 | GEO
Project description:In order to analyze the regulatory effects of UII and GPR14 on gene transcription in Mc903-induced atopic dermatitis skin, ear skin collected from MC903 chronic itch mouse model on day 13 was used for in-depth analysis and sequencing of skin gene expression. The effect of GSK1562590 on the expression of pruritus and inflammatory factors in dermatitis was detected by RNA-seq.
2023-06-16 | GSE226669 | GEO