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Mechanosensitive proteins are sensitized in myelinated afferents following in vivo inflammation

ABSTRACT: Here we identified two populations of myelinated sensory neurons that display markedly different phenotypes in terms of their action potential characteristics and responses to mechanical stimuli based on their expression of Calcitonin Gene-Related Peptide (CGRP). Myelinated neurons that did not express CGRP responded to mechanical stimuli with significantly larger currents during whole-cell voltage clamp recordings than their CGRP-positive counterparts, regardless of whether these neurons projected to the dorsal hindpaw skin or the gastrocnemius muscle. Importantly, this discrepancy could not be explained by a differential expression of mechanosensitive or mechanically-gated proteins like Stoml3 or Piezo2. Following inflammation of the skin or muscle, myelinated neurons demonstrated a sensitization to mechanical stimuli characterized by increased current amplitudes. Interestingly, myelinated neurons expressing CGRP are sensitized to mechanical stimuli following cutaneous inflammation of the paw, while myelinated neurons that do not express CGRP are sensitized to mechanical stimuli following inflammation of the gastrocnemius muscle. Microarray data was obtained from these populations by first using Fluorescence-Activated Cell Sorting (FACS) to separate the populations of interest.

ORGANISM(S): Mus musculus

PROVIDER: GSE65613 | GEO | 2015/11/06

SECONDARY ACCESSION(S): PRJNA274449

REPOSITORIES: GEO

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Mechanosensitive proteins are sensitized in myelinated afferents following in vivo inflammation

Project description:Here we identified two populations of myelinated sensory neurons that display markedly different phenotypes in terms of their action potential characteristics and responses to mechanical stimuli based on their expression of Calcitonin Gene-Related Peptide (CGRP). Myelinated neurons that did not express CGRP responded to mechanical stimuli with significantly larger currents during whole-cell voltage clamp recordings than their CGRP-positive counterparts, regardless of whether these neurons projected to the dorsal hindpaw skin or the gastrocnemius muscle. Importantly, this discrepancy could not be explained by a differential expression of mechanosensitive or mechanically-gated proteins like Stoml3 or Piezo2. Following inflammation of the skin or muscle, myelinated neurons demonstrated a sensitization to mechanical stimuli characterized by increased current amplitudes. Interestingly, myelinated neurons expressing CGRP are sensitized to mechanical stimuli following cutaneous inflammation of the paw, while myelinated neurons that do not express CGRP are sensitized to mechanical stimuli following inflammation of the gastrocnemius muscle. Microarray data was obtained from these populations by first using Fluorescence-Activated Cell Sorting (FACS) to separate the populations of interest. 15 different samples were analyzed, 3 biological replicates for each group (5 groups: saline paw-injected, CFA paw-injected, saline muscle-injected, acid muscle-injected, and CFA muscle-injected). The saline injected groups (paw and muscle) are considered controls.

2015-11-06 | E-GEOD-65613 | biostudies-arrayexpress

Mus musculus

Project description:Mechanosensitive proteins are sensitized in myelinated afferents following in vivo inflammation

| PRJNA274449 | ENA

The neuroimmune CGRP-RAMP1 axis tunes cutaneous adaptive immunity to the microbiota

Project description:The somatosensory nervous system surveils external stimuli at barrier tissues, regulating innate immune cells under infection and inflammation. The roles of sensory neurons in controlling the adaptive immune system, and more specifically immunity to the microbiota, however, remain elusive. Here, we identified a novel mechanism for direct neuroimmune communication between commensal-specific T lymphocytes and somatosensory neurons mediated by the neuropeptide calcitonin gene-related peptide (CGRP) in the skin. Intravital imaging revealed that commensal-specific T cells are in close proximity to cutaneous nerve fibers in vivo. Correspondingly, we observed upregulation of the receptor for the neuropeptide CGRP, RAMP1, in CD8+ T lymphocytes induced by skin commensal colonization. Neuroimmune CGRP-RAMP1 signaling axis functions in commensal-specific T cells to constrain Type 17 responses and moderate the activation status of microbiota-reactive lymphocytes at homeostasis. As such, modulation of neuroimmune CGRP-RAMP1 signaling in commensal-specific T cells shapes the overall activation status of the skin epithelium, thereby impacting the outcome of responses to insults such as wounding. The ability of somatosensory neurons to control adaptive immunity to the microbiota via the CGRP-RAMP1 axis underscores the various layers of regulation and multisystem coordination required for optimal microbiota-reactive T cell functions under steady state and pathology.

2024-02-21 | GSE253063 | GEO

The neuroimmune CGRP-RAMP1 axis tunes cutaneous adaptive immunity to the microbiota.

2024-02-21 | GSE253041 | GEO

Time-course transcriptomic profiling of C57BL/6 mouse neurons from the dorsal root ganglion before and after a carrageenan injection into the left hind paw

Project description:Carrageenan injection induces tissue inflammation and high mechanosensitivity. Dorsal root ganglions contain the cellular body of the sensory neurons which project their axon to the periphery, monitoring this inflammation and transmitting the mechanical stimuli to the spinal cord. To explore whether the sensory neurons underwent transcriptional changes and how long these changes lasted, we injected carrageenan into the left hind paw of mice and sequenced the dorsal root ganglions related to this area 1, 3 and 30 days after the injection.

2020-11-19 | GSE161764 | GEO

Dendrite intercalation between epidermal cells tunes nociceptor sensitivity to mechanical stimuli in Drosophila larvae

Project description:An animal’s skin provides a first point of contact with the sensory environment, including noxious cues that elicit protective behavioral responses. Nociceptive somatosensory neurons densely innervate and intimately interact with epidermal cells to receive these cues, however the mechanisms by which epidermal interactions shape processing of noxious inputs is still poorly understood. Here, we identify a role for dendrite intercalation between epidermal cells in tuning sensitivity of Drosophila larvae to noxious mechanical stimuli. In wild-type larvae, dendrites of nociceptive class IV da neurons intercalate between epidermal cells at apodemes, which function as body wall muscle attachment sites, but not at other sites in the epidermis. From a genetic screen we identified miR-14 as a regulator of dendrite positioning in the epidermis: miR-14 is expressed broadly in the epidermis but not in apodemes, and miR-14 inactivation leads to excessive apical dendrite intercalation between epidermal cells. We found that miR-14 regulates expression and distribution of the epidermal Innexins ogre and Inx2 and that these epidermal gap junction proteins restrict epidermal dendrite intercalation. Finally, we found that altering the extent of epidermal dendrite intercalation had corresponding effects on nociception: increasing epidermal intercalation sensitized larvae to noxious mechanical inputs and increased mechanically evoked calcium responses in nociceptive neurons, whereas reducing epidermal dendrite intercalation had the opposite effects. Altogether, these studies identify epidermal dendrite intercalation as a mechanism for mechanical coupling of nociceptive neurons to the epidermis, with nociceptive sensitivity tuned by the extent of intercalation.

2024-03-31 | GSE262604 | GEO

NGF-induced gene expression in silent nociceptors

Project description:Silent nociceptors are sensory afferents that are insensitive to noxious mechanical stimuli under normal conditions but become sensitized to such stimuli during inflammation. We had previously shown that mouse silent nociceptors express the nicotinic acetylcholine receptor alpha-3 subunit (CHRNA3) and can thus readily be identified in Tg(Chrna3-EGFP)BZ135Gsat reporter mice (Prato et al. Cell Reports 2017). Most importantly, we had shown that CHRNA3+ slient nociceptors acquire mechanosensitivity upon treatment with the inflammatory mediator nerve growth factor and demonstrated that this process requires de-novo gene transcription. Here, we performed paired-end RNA-sequencing to identify transcripts that might be involved in the acquisition of mechanosenstivity in mouse silent nociceptors.

2022-12-01 | GSE199580 | GEO

Transcriptional characterization of major cellular compartments within muscle tissue at homeostasis and after acute injury in mice

Project description:A distinct population of Foxp3+CD4+ regulatory T (Treg) cells promotes repair of acutely or chronically injured skeletal muscle. The accumulation of these cells depends critically on interleukin (IL)-33 produced by local mesenchymal stromal cells (mSCs). An intriguing physical association between muscle nerves, IL-33+ mSCs and Tregs has been reported, and begs a deeper exploration of this cell triumvirate. Here we evidence a striking proximity between IL-33+ muscle mSCs and both large-fiber nerve bundles and small-fiber sensory neurons; report that muscle mSCs transcribe an array of genes encoding neuropeptides, neuropeptide receptors and other nerve-related proteins; define muscle mSC subtypes that express both IL-33 and the receptor for the calcitonin-gene-related peptide (CGRP); and demonstrate that up- or down- tuning of CGRP signals augments or diminishes, respectively, IL-33 production by muscle mSCs and later accumulation of muscle Tregs. Indeed, a single injection of CGRP induced much of the genetic program elicited in mSCs early after acute skeletal muscle injury. These findings highlight neural/stromal/immune-cell cross-talk in tissue repair, suggesting future therapeutic approaches.

2020-02-10 | GSE143426 | GEO

Transcriptional characterization of mesenchymal stromal cells isolated from muscle and lymph node at homeostasis in mice

2020-02-10 | GSE143425 | GEO

Role of CGRP on muscle mesenchymal stromal cells in mice

2020-02-10 | GSE143424 | GEO