The neuroimmune CGRP-RAMP1 axis tunes cutaneous adaptive immunity to the microbiota.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1063694 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27499239.fastq.gz | Fastqsanger.gz | |||
| SRR27499240.fastq.gz | Fastqsanger.gz | |||
| SRR27499241.fastq.gz | Fastqsanger.gz | |||
| SRR27499242.fastq.gz | Fastqsanger.gz | |||
| SRR27499243.fastq.gz | Fastqsanger.gz |
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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
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 | GSE253041 | GEO
Project description:The neuroimmune CGRP-RAMP1 axis tunes cutaneous adaptive immunity to the microbiota
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Project description:Endometriosis is a debilitating and painful gynecological inflammatory disease affecting approximately 15% of women. Current treatments are ineffective for a significant fraction of patients, underscoring the need for new medical therapies with long-term benefits. Given the relevance of neuroimmune communication in different disease outcomes, we investigated the role of CGRP-mediated neuroimmune communication in endometriosis. We found that mouse and human endometriosis lesions contained CGRP and RAMP1. In mice, nociceptor ablation reduced pain, monocyte recruitment, and lesion size, suggesting that nociceptor activation and neuropeptide release contribute to endometriosis lesion growth and pain. In vitro, CGRP-induced pro-endometriosis macrophages (PEMs) showed impaired efferocytosis and supported endometrial cell growth in a RAMP1-dependent manner. Treatment with FDA-approved drugs that block CGRP-RAMP1 signaling reduced mechanical hyperalgesia, spontaneous pain, and lesion size in mice. Altogether, our data demonstrates the effectiveness, cellular mechanisms and pre-clinical safety of non-hormonal and non-opioid CGRP/RAMP1 blocking therapies, which may lead to clinical benefit for endometriosis patients.
2025-08-09 | GSE274685 | GEO
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 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. The 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.
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Project description:Innate and adaptive lymphocytes work in concert to maintain tissue homeostasis and to mediate host defense at mucosal barriers. Herein, we used single cell analysis to show substantial diversity of gene expression in ILCs and T helper cells during a helminth infection in the lung. Notably, we found that the Calca gene, which is spliced to generate the neuropeptide CGRP, was selectively transcribed in ILC2s and Th2 cells in an activation dependent manner. The Calca locus acquired chromatin accessibility at the ILC2 precursor stage and is pre-programmed for rapid production of CGRP upon ILC2 activation. CGRP globally antagonized actions of neuromedin U (NMU) and the alarmin IL-33. However, CGRP selectively acted in concert with NMU and IL-33 to promote IL-5 expression, but not IL-13. The complex interplay among neuropeptides and alarmin fine-tunes type 2 immune responses and will undoubtedly become more relevant as therapeutic neuropeptide blockade advances in the clinic.
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Project description:Study of the expression profiles of brain regions (amygdala, hippocampus and cerebral cortex) and trigeminal ganglia collected from rats treated with fremanezumab, an anti-calcitonin gene related peptide (CGRP) mAb, used for the prevention of migraine.
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