Calcitonin gene-related peptide is a key neurotransmitter in the neuro-immune axis

Abstract

The question of how the neural and immune systems interact in host defense is important, integrating a system that senses the whole body with one that protects. Understanding the mechanisms and routes of control could produce novel and powerful ways of promoting and enhancing normal functions as well as preventing or treating abnormal functions. Fragmentation of biological research into specialities has resulted in some failures in recognizing and understanding interactions across different systems and this is most striking across immunology, hematology, and neuroscience. This reductionist approach does not allow understanding of the in vivo orchestrated response generated through integration of all systems. However, many factors make the understanding of multisystem cross-talk in response to a threat difficult, for instance the nervous and immune systems share communication molecules and receptors for a wide range of physiological signals. But, it is clear that physical, hard-wired connections exist between the two systems, with the key link involving sensory, unmyelinated nerve fibers (c fibers) containing the neuropeptide calcitonin gene-related peptide (CGRP), and modified macrophages, mast cells and other immune and host defense cells in various locations throughout the body. In this review we will therefore focus on the induction of CGRP and its key role in the neuroimmune axis.

Opposing expression gradients of calcitonin‐related polypeptide alpha (Calca/Cgrpα) and tyrosine hydroxylase (Th) in type II afferent neurons of the mouse cochlea

“…One such gene, Calca , encoding for calcitonin gene‐related peptide alpha (CGRPα), is expressed in a wide variety of neuronal and non‐neuronal cell types, ranging from keratinocytes to primary afferent neurons and spinal motor neurons (Russell, King, Smillie, Kodji, & Brain, ). CGRP is a potent vasodilator and mediates neuronal‐immune system communication (Assas, Pennock, & Miyan, ). CGRP is expressed specifically in small C and Aδ neurons of dorsal root ganglia.…”

Recommendations on the Use of Anti‐CGRP Monoclonal Antibodies in Children and Adolescents

“…CGRP plays a role in the neuro‐immune axis, with CGRP‐containing nerve fibers located in the thymus, bone marrow, spleen, skin, lymph nodes, lungs, and gastrointestinal tract . CGRP receptors are present on lymphocytes, macrophages, mast cells and dendritic cells, and, in turn, these cells can synthesize CGRP . CGRP exerts a variety of pro‐ and anti‐inflammatory actions, and is hypothesized to exert nervous system control over immune function .…”

“…CGRP receptors are present on lymphocytes, macrophages, mast cells and dendritic cells, and, in turn, these cells can synthesize CGRP . CGRP exerts a variety of pro‐ and anti‐inflammatory actions, and is hypothesized to exert nervous system control over immune function . Reassuringly, adult participants in trials to date have not developed serious infections.…”

Sensory neuron regulation of gastrointestinal inflammation and bacterial host defence

“…monocytes, T cells, B cells) release CGRP or regulate sensory neuron expression of CGRP [92]. CGRP plays important roles in lymphocyte maturation, proliferation, migration, antigen presentation, and cytokine production (for an extensive review, see [93]).…”