An Integrated View on Neuronal Subsets in the Peripheral Nervous System and Their Role in Immunoregulation.

Manuel O Jakob,Shaira Murugan,Christoph S N Klose,Michael Kofoed-Branzk,Divija Deshpande

doi:10.3389/fimmu.2021.679055

Abstract

The peripheral nervous system consists of sensory circuits that respond to external and internal stimuli and effector circuits that adapt physiologic functions to environmental challenges. Identifying neurotransmitters and neuropeptides and the corresponding receptors on immune cells implies an essential role for the nervous system in regulating immune reactions. Vice versa, neurons express functional cytokine receptors to respond to inflammatory signals directly. Recent advances in single-cell and single-nuclei sequencing have provided an unprecedented depth in neuronal analysis and allowed to refine the classification of distinct neuronal subsets of the peripheral nervous system. Delineating the sensory and immunoregulatory capacity of different neuronal subsets could inform a better understanding of the response happening in tissues that coordinate physiologic functions, tissue homeostasis and immunity. Here, we summarize current subsets of peripheral neurons and discuss neuronal regulation of immune responses, focusing on neuro-immune interactions in the gastrointestinal tract. The nervous system as a central coordinator of immune reactions and tissue homeostasis may predispose for novel promising therapeutic approaches for a large variety of diseases including but not limited to chronic inflammation.

Highlights

The nervous system in multi-cellular organisms consists of a complex network of neurons, which can rapidly and precisely transmit signals
We noticed that certain genes are more ubiquitously expressed by different neuronal subpopulations and may be involved in different functions depending on the neuronal subtype
Our review combines several datasets and allows for the identification of neuronal subtypes based on genes expressed, morphology and function

Summary

Introduction

The nervous system in multi-cellular organisms consists of a complex network of neurons, which can rapidly and precisely transmit signals. The nervous system is organized in circuits linking afferent sensory input with a broad array of reactions at effector sites. In this way, the nervous system coordinates physiological functions, such as behavior, motor functions, blood pressure and hormone release (1–4). The somatic nervous system consists of peripheral somatosensory nerves, which convey afferent signals and efferent nerves controlling motor functions, e.g. regulating movements of extremities. The parasympathetic and sympathetic nervous system are typical functional counter players for opposing physiological functions: the rest-and-digest (parasympathetic nervous system) and the fightor-flight reaction (sympathetic nervous system). Loss of the intrinsic ENS can be disastrous, as shown in Hirschsprung or Chagas disease, where intestinal motor functions are significantly reduced or absent (7, 8)

Objectives

Conclusion