Neuro–Immune Cell Units: A New Paradigm in Physiology

Abstract

The interplay between the immune and nervous systems has been acknowledged in the past, but only more recent studies have started to unravel the cellular and molecular players of such interactions. Mounting evidence indicates that environmental signals are sensed by discrete neuro–immune cell units (NICUs), which represent defined anatomical locations in which immune and neuronal cells colocalize and functionally interact to steer tissue physiology and protection. These units have now been described in multiple tissues throughout the body, including lymphoid organs, adipose tissue, and mucosal barriers. As such, NICUs are emerging as important orchestrators of multiple physiological processes, including hematopoiesis, organogenesis, inflammation, tissue repair, and thermogenesis. In this review we focus on the impact of NICUs in tissue physiology and how this fast-evolving field is driving a paradigm shift in our understanding of immunoregulation and organismal physiology.

Stability and dynamics of the human gut microbiome and its association with systemic immune traits

“…In previous association studies, the metabolic pathway "PWY-5022 4-aminobutanoate degradation V", responsible for the breakdown of GABA into the SCFA butyrate, was identified as causally associated with increased insulin secretion following an oral glucose challenge (Sanna et al, 2019). Additionally, neuro-immunology is an emerging focus for disease pathogenesis, one that might be influenced by commensal metabolic pathways and bears further investigation (Godinho-Silva et al, 2019). Moving forward, as sample sizes increase, new microbe x immune interactions will continue to be uncovered.…”

Sensory Neurons Innervate Peripheral Lymph Nodes and Locally Regulate Gene Expression in Postsynaptic Endothelium, Stromal Cells, and Innate Leukocytes

“…Indeed, neuro-immune interactions have been intensively investigated in a number of settings, especially in the central nervous system (CNS) (Klein et al, 2017;Norris and Kipnis, 2019;Prinz and Priller, 2017). Moreover, 50 several recent studies have uncovered evidence for bidirectional communication between the peripheral nervous system (PNS) and the immune system in the spleen, bone marrow, intestine, airways, lungs and skin (Baral et al, 2019;Foster et al, 2017;Godinho-Silva et al, 2019;McMahon et al, 2015;Ordovas-Montanes et al, 2015;Veiga-Fernandes and Mucida, 2016). However, the mechanisms and consequences of these multi-facetted interactions are still poorly understood.…”

“…Motor commands are relayed from the CNS to skeletal muscles and visceral organs, and executed by spinal motor 60 neurons and sympathetic/parasympathetic neurons, respectively. The autonomic motor neuron (i.e., sympathetic/parasympathetic neurons), have long been recognized for their impact on immunity (Chavan et al, 2017;Godinho-Silva et al, 2019), whereas the role of the somatosensory PNS as a critical immunomodulatory component has been appreciated only recently.…”

Antibody responses to immunization require sensory neurons

“…Although the immune and nervous systems clearly perform unique functions, they communicate and regulate each other to maintain homeostasis. Several studies have identified bidirectional crosstalk between nervous system and immune system in healthy state and pathologies in numerous conditions, including chronic inflammatory disorders, acute inflammatory conditions, autism, multiple sclerosis, and cancer (Louveau et al, 2015;Baral et al, 2018;Veiga-Fernandes and Mucida, 2016;Godinho-Silva et al, 2019). Recent studies have also revealed that specific anatomical locations of neuro-immune interactions may serve as important immunoregulatory hubs (Huang et al, 2019;Godinho-Silva et al, 2019;Veiga-Fernandes and Pachnis, 2017).…”