SAMN39991917
External Id
Monash Univeristy
INSDC center name
2025-03-02T00:50:22.903Z
INSDC first public
2025-03-02T00:50:22.903Z
INSDC last update
live
INSDC status
Model organism or animal
NCBI submission model
Model.organism.animal.1.0
NCBI submission package
8-12 weeks
age
2023-10-21
collection_date
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.
description
8-12 weeks
dev_stage
Australia
geo_loc_name
Mus musculus
http://purl.obolibrary.org/obo/NCBITaxon_10090
organism
male
sex
eukaryote
strain
Bone marrow
tissue
Macrophage from Mus musculus bone marrow
title