Innervation of lymphoid organs: Clinical implications

Host defense against pathogens is regulated by cross-talk between two major adaptive systems of the body-the nervous and immune systems. This bidirectional communication is essential for maintaining homeostasis. Sympathetic nerves that innervate lymphoid tissues provide one of the major outflows from the brain to regulate tissue repair and host defense. This review focuses on the role of (sympathetic nervous system) SNS in neuroimmune regulation, an area that has received much less attention than the other major immunoregulatory pathway, the hypothalamo-pituitary-adrenal (HPA) axis. Research over the past 25 years has demonstrated that norepinephrine (NE) fulfills the criteria for neurotransmission in lymphoid tissue, with both primary and secondary immune organs receiving an extensive supply of sympathetic nerves that directly contact with immunocytes. Under stimulation, NE released from terminals in secondary lymphoid organs interacts with adrenergic receptors (AR) expressed on immune cells to affect the development, trafficking, circulation, proliferation, cytokine production, and the functional activity of variety of lymphoid and myeloid cells. Our knowledge of the role of sympathetic nerves in modulating hematopoietic functions of primary lymphoid organs (bone marrow and thymus) and mucosal immunity are extremely limited. While the immune system is not absolutely dependent upon signals from the brain to function, sympathetic-immune modulation may drive host defense toward protection against, or progression toward, immune-related diseases. Additionally, signals from the (SNS) may enhance immune readiness during disease- or injury-induced 'fight-or-flight' responses. A better understanding of neural-immune interactions may foster the development of strategies for treating immune-mediated diseases, particularly where neuroimmune cross-talk may be dysregulated.