Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs

Abstract

The central nervous system (CNS) influences the immune system generally by regulating the systemic concentration of humoral substances (e.g., cortisol and epinephrine), whereas the peripheral nervous system (PNS) communicates specifically with the immune system according to local interactions/connections. An imbalance between the components of the PNS might contribute to pathogenesis and the further development of certain diseases. In this review, we have explored the “thread” (hardwiring) of the connections between the immune system (e.g., primary/secondary/tertiary lymphoid tissues/organs) and PNS (e.g., sensory, sympathetic, parasympathetic, and enteric nervous systems (ENS)) in health and disease in vitro and in vivo. Neuroimmune cell units provide an anatomical and physiological basis for bidirectional crosstalk between the PNS and the immune system in peripheral tissues, including lymphoid tissues and organs. These neuroimmune interactions/modulation studies might greatly contribute to a better understanding of the mechanisms through which the PNS possibly affects cellular and humoral-mediated immune responses or vice versa in health and diseases. Physical, chemical, pharmacological, and other manipulations of these neuroimmune interactions should bring about the development of practical therapeutic applications for certain neurological, neuroimmunological, infectious, inflammatory, and immunological disorders/diseases.

Aging brain: exploring the interplay between bone marrow aging, immunosenescence, and neuroinflammation

“…Remarkably, apart from immune cells, a variety of other cell types such as mesenchymal stromal/stem cells, fibroblasts, endothelial cells, osteoblasts, neurons, and Schwann cells demonstrate notable immune functions. These functions include the secretion of cytokines, chemokines, and growth factors, as well as the facilitation of inflammation, antigen presentation, immunosuppression, and antimicrobial effects, particularly in response to conditions like infection and inflammation ( 70 , 74 ). Aging processes in these cells may lead to functional impairments, resulting in disturbances in their activity and function, thus contributing to age-related diseases.…”

“…The complex interplay between the immune and nervous systems manifests additionally in the concept of neuroimmune cell units, where immune cells closely interact with neurons and glial cells, shaping the dynamics of neuroinflammation and influencing disease progression in various neurological disorders ( 74 , 75 ). In this regard, neuroimmune cell units are emerging as pivotal coordinators of diverse physiological processes, encompassing hematopoiesis, inflammatory responses, and tissue regeneration ( 76 ).…”

“…These specialized structures facilitate direct communication and coordination between the two systems, with immune cells such as microglia, B- and T cells, dendritic cells, and macrophages interacting closely with neurons and other glial cells. These interactions, occurring through physical contacts or synapse-like connections, involve the exchange of signaling molecules, including cytokines, chemokines, neurotransmitters, and other immune modulators ( 7 , 74 ). Neuroimmune cell units are believed to exert a significant influence on regulating neuroinflammatory responses, modulating neuroimmune signaling, and impacting disease progression in various neurological disorders ( 74 ).…”

“…These interactions, occurring through physical contacts or synapse-like connections, involve the exchange of signaling molecules, including cytokines, chemokines, neurotransmitters, and other immune modulators ( 7 , 74 ). Neuroimmune cell units are believed to exert a significant influence on regulating neuroinflammatory responses, modulating neuroimmune signaling, and impacting disease progression in various neurological disorders ( 74 ).…”

“…Conversely, neuroinflammation in the CNS can also impact immune cell function, potentially exacerbating age-related changes in hematopoiesis and immune cell production. Moreover, emerging evidence suggests bidirectional communication between the bone marrow and the CNS, mediated by factors such as cytokines, chemokines, and extracellular vesicles ( 11 , 74 ). These communication pathways may play a crucial role in coordinating immune responses between the bone marrow and the CNS, influencing the progression of neuroinflammation and neurological diseases.…”