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Nociceptive neurons interact with gastric cancer cells via a CGRP/Ramp1 axis to promote tumor progression

ABSTRACT: Nociceptive neurons interact with gastric cancer cells via a CGRP/Ramp1 axis to promote tumor progression

PROVIDER: PRJNA1018958 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26113203_1.fastq.gz	Fastqsanger.gz
	SRR26113203_2.fastq.gz	Fastqsanger.gz

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Nociceptive neurons interact with gastric cancer cells via a CGRP/Ramp1 axis to promote tumor progression

Project description:To determine how DRG affects mouse gastric cancer cells, we cocultured GC cells with DRG

2024-11-24 | GSE243578 | GEO

Nociceptive nerves regulate haematopoietic stem cell mobilization

Project description:Nociceptive neuropeptide CGRP acts directly on HSCs via the its receptor RAMP1/CALCRL, to promote egress by activating Gαs/Adenylyl cyclase/cAMP pathway.

2020-10-12 | GSE156449 | GEO

CGRP sensory neurons promote tissue healing by modulating neutrophils and macrophages

Project description:Since the immune system plays a critical role in orchestrating tissue healing, regenerative strategies that control immune components have proven effective. This is particularly relevant when immune dysregulation resulting from conditions such as diabetes or advanced age impairs tissue healing following injury. Nociceptive sensory neurons play a crucial role as immunoregulators, exerting both protective and harmful effects depending on the context. However, how neuro-immune interactions impact tissue repair and regeneration after acute injury is unclear. Here, we show that Nav1.8+ nociceptor ablation impairs skin wound repair and muscle regeneration after acute tissue injuries. Nociceptor endings grow into injured skin and muscle tissues and signal to immune cells through the neuropeptide calcitonin gene-related peptide (CGRP) during the healing process. CGRP acts via receptor activity modifying protein 1 (RAMP1) on neutrophils and macrophages to inhibit recruitment, accelerate death, enhance efferocytosis, and polarise macrophages towards a pro-repair phenotype. CGRP effects on neutrophils and macrophages are mediated via thrombospondin-1 release and its subsequent autocrine/paracrine effects. In mice without nociceptors and diabetic mice with peripheral neuropathies, delivering an engineered version of CGRP accelerated wound healing and promoted muscle regeneration. Harnessing neuro-immune interactions holds potential to treat non-healing tissues where dysregulated neuro-immune interactions impair tissue healing.

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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.

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

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Anti-CGRP Monoclonal Antibodies Counteract Interoceptive Awareness of Malaise

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Expression Data from fracture calli of alpha-CGRP deficient mice

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Bulk RNA-sequencing of synovial macrophages (CGRP stimulation)

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Neuropeptide CGRP limits ILC2 responses and constrains type 2 inflammation

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Effect of nociceptive neuropeptides on dendritic cells

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