Nppb Neurons Are Sensors Of Mast Cell-Induced Itch
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ABSTRACT:
PROVIDER: PRJNA516935 | ENA |
REPOSITORIES: ENA
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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: Not available
| S-EPMC6490177 | biostudies-literature
Project description:We performed RNA-seq to identify transcriptional profiles of itch-activated CeA neurons. To do this, we crossed FosTRAP mice to the Cre-dependent tdTomato flox-stop reporter line as described above. We then injected chloroquine into the nape of the neck, paired with injection of 4-OHT to FosTRAP expression of tdTomato in itch-activated neurons. The CeA was harvested, the cells dissociated and sorted by FACS, and tdTomato+ cells were compared to TdTomato- cells.
2020-04-23 | GSE130268 | GEO
Project description:Transcriptional Idenetity of Itch-activated Central Amygdala Neurons
| PRJNA534481 | 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 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 the present study, RNA-seq were performed To identify clinical relevance of PLAUR, a putative Serpin E1 receptor, in cutaneous itch signaling and crosstalk pathways with other critical itch modulators.mRNA profiles were generated by deep sequencing, in triplicate, using MGISEQ-2000. Our experiment showed Serpin E1-treatment further led to a marked upregulation of TLR2 transcript in mDRG neurons, along with enhanced transcription of cosignaling proteins belonging to pro-inflammatory signaling pathways including NF-κB signaling proteins. We next investigated the consequence of TLR2 activation in mTGNs using the TLR agonists, Pam3CSK4 (TLR1/2 agonist), FSL-1 (TLR2/6 agonist), or vehicle. Among these transcripts, TLR2 was found upregulated strongest by both TLR2 agonists suggesting a selfenhancing feedback loop of TLR2 activation.The PLAUR-TLR2 axis promotes cutaneous inflammation and itch, both feeding into an aggravation of AD. This finding might help us to better understand the skin-nerve communication in itch circuits.
2022-08-03 | GSE189333 | GEO
Project description:MrgprD-expressing neurons maintain cutaneous mast cell homeostasis
| PRJNA600963 | ENA
Project description:We found that the E3 ubiquitin ligase Itch significantly affects early B-cell differentiation. To explore the role of Itch in late B-cell differentiation, we sorted B cells from WT and Itch KO mice. To explore the effect of Itch deficency on gene expression, we determined mRNA profiles in B cells from WT and Itch KO mice by RNA-seq. RNA-seq was done with an Illumina HiSeq 2500 instrument at GENEWIZ, Suzhou, China.
2020-03-01 | E-MTAB-8273 | biostudies-arrayexpress
Project description:We found that the E3 ubiquitin ligase Itch significantly affects early B-cell differentiation. To explore the role of Itch in late B-cell differentiation, we sorted B cells from WT and Itch cKO mice. To explore the effect of Itch deficency on gene expression, we determined mRNA profiles in B cells from WT and Itch cKO mice by RNA-seq. RNA-seq was done with an Illumina HiSeq 2500 instrument at GENEWIZ, Suzhou, China.
2020-03-01 | E-MTAB-8281 | biostudies-arrayexpress
Project description:The paralogous genes Nppa and Nppb are organized in an evolutionary conserved cluster and are a valuable model to study coregulation and regulatory landscape organization during heart development and disease. Here, we analyzed the chromatin conformation, epigenetic status and enhancer potential of sequences of the Nppa-Nppb cluster in vivo. Our data indicate that the regulatory landscape of the cluster is present within a 60 kbp domain centered around Nppb. Both promoters and several potential regulatory elements interact with each other in a similar manner in different tissues and developmental stages. The distribution of H3K27ac and the association of Pol2 across the locus changed during cardiac hypertrophy, revealing their potential involvement in stress-mediated gene regulation. In summary, the developmental regulation and stress-response of the Nppa-Nppb cluster involve the concerted action of multiple enhancers and epigenetic changes distributed across a structurally rigid regulatory domain. We have used 4C-seq on several viewpoints around the Nppa-Nppb gene cluster in the heart and liver samples to investigate the role of chromatin conformation on regulation of Nppa and Nppb expression during heart development and disease.
2016-07-02 | E-GEOD-81057 | biostudies-arrayexpress