Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA356278 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5077220.fastq.gz | Fastqsanger.gz | |||
| SRR5077221.fastq.gz | Fastqsanger.gz | |||
| SRR5077214.fastq.gz | Fastqsanger.gz | |||
| SRR5077215.fastq.gz | Fastqsanger.gz | |||
| SRR5077216.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch [6 NaV1.8+ Il4raF/F mice treated with MC903 compared to skin from 4 littermates]
| PRJNA391520 | ENA
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 type 2 cytokines directly stimulate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling. Based on these observations, we show that patients with recalcitrant chronic itch markedly improve when treated with JAK inhibitors in proof-of-concept clinical studies. 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 | GSE100397 | 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:In naïve individuals, sensory neurons directly detect and respond to allergens, leading both to the sensation of itch and the activation of local innate immune cells, which initiate the allergic immune response1,2. In the setting of chronic allergic inflammation, immune factors prime sensory neurons, causing pathologic itch3-7. While these bidirectional neuroimmune circuits drive responses to allergens, whether immune cells regulate the set-point for neuronal activation by allergens in the naïve state is unknown. Here we describe a T cell-IL-3 signaling axis that controls the allergen responsiveness of cutaneous sensory neurons. We define a poorly characterized epidermal T cell subset8, termed GD3 cells, that produces its hallmark cytokine IL-3 to promote allergic itch and the initiation of the allergic immune response. Mechanistically, IL-3 acts on Il3ra-expressing sensory neurons in a JAK2-dependent manner to lower their threshold for allergen activation without independently eliciting itch. This T cell-IL-3 signaling axis further acts via STAT5 to promote neuropeptide production and the initiation of allergic immunity. These results reveal an endogenous immune rheostat that sits upstream of and governs sensory neuronal responses to allergens upon first exposure. This pathway may explain individual differences in allergic susceptibility and opens novel therapeutic avenues for treating allergic diseases.
2024-06-11 | GSE223220 | GEO
Project description:In the present study, RNA-seq were performed To explore biological significance of IL-27 and BST2 in the neuro-cutaneous signaling network of chronic itch. mRNA profiles were generated by deep sequencing, in triplicate, using MGISEQ-2000. We found that both human keratinocytes and murine sensory neurons responded to IL-27 and BST2, resulting in enrichment of genes promoting itch and inflammation. IL-27-BST2 signaling pathway activation promotes cutaneous inflammation and itch, both leading into an aggravation of AD. This finding might help us to better understand the immune-neuro-modulatory mechanism in itch circuits
2024-03-05 | GSE188242 | GEO
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:Itch is an unpleasant skin sensation which can be triggered by exposure to many chemicals including those released by mast cells. The Nppb-expressing class of sensory neurons when activated elicit scratching responses in mice, however, it is unclear which itch-inducing agents stimulate these cells and the receptors involved. Here, we identify receptors expressed by Nppb-neurons and demonstrate the functional importance of these receptors as sensors of endogenous pruritogens released by mast cells. Our search for receptors in Nppb-neurons revealed that they express leukotriene, serotonin, and sphingosine-1-phosphate receptors. Targeted cell ablation, calcium imaging of primary sensory neurons, and conditional receptor knockout studies demonstrate that these receptors induce itch by the direct stimulation of Nppb-neurons and neurotransmission through the canonical GRP-dependent spinal cord itch pathway. Together our results define a molecular and cellular pathway for mast cell-induced itch.
2019-03-26 | GSE125626 | GEO
Project description:We performed RNA sequencing of genetically labeled MrgprA3+ neurons under both naïve and allergic contact dermatitis conditions. 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 a 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.
2020-03-13 | GSE146876 | GEO
Project description:Allergic conjunctivitis is a chronic inflammatory disease that is characterized by severe itch in the conjunctiva; but how neuro-immune interactions shape the pathogenesis of severe itch remains unclear. We identified a subset of memory-type pathogenic Th2 cells that preferentially expressed Il1rl1-encoding ST2 and Calca-encoding calcitonin gene-related peptide (CGRP) in the inflammatory conjunctiva using a single-cell analysis. The IL-33-ST2 axis in memory Th2 cells controlled the axonal elongation of the peripheral sensory C-fiber and the induction of severe itch. Pharmacological blockade and genetic deletion of CGRP signaling in vivo attenuated scratching behavior. The analysis of giant papillae from patients with severe allergic conjunctivitis revealed ectopic lymphoid structure formation with the accumulation of IL-33-producing epithelial cells and CGRP-producing pathogenic CD4+ T cells accompanied by peripheral nerve elongation. Thus, the IL-33-ST2-CGRP axis directs severe itch with neuro-reconstruction in the inflammatory conjunctiva and is a potential therapeutic target for severe itch in allergic conjunctivitis.
2022-05-20 | GSE203217 | GEO
Project description:By utilizing single-cell analysis of neurons that are produced at day 9 of mESC differentiation period (day 9) under the developmentally relevent signals- Retinoic acid and BMP4, we identified that our protocol can generate all major sensory neuron subtypes that are required for relaying sensation like pain, itch, heat and proprioception in the spinal cord. This analysis also identified functional features in each neuronal subtypes, confirming the bonafide status of the in vitro derived sensory neurons.
2022-07-09 | GSE185890 | GEO