Neuro-immune interactions
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INTRODUCTION
Neuro-immune interactions J. David Farrar 1 Received: 28 October 2020 / Accepted: 4 November 2020 / Published online: 26 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
The immune system harbors immense potential energy, which must be harnessed even in the face of the most egregious assaults by pathogenic organisms. From the outside, it may seem that immunity operates on a binary ON/OFF switch. In the absence of infection, the immune system seems invisible. Challenge it with even a single danger signal, and the kinetic energy of immune cells appears to be released in full force. In reality, there are intrinsic checks and balances that control the magnitude of immune responsiveness, such as central tolerance, suppressive cytokines, Treg cells, and checkpoint inhibitors, to name a few. Collectively, these control mechanisms effectively stabilize the immune system so that self/non-self discrimination acts as the main switch to engage a response. While these intrinsic regulatory pathways control major immune processes such as antigen recognition, immune homeostasis is an important facet of immune regulation that is often under appreciated. Both immune intrinsic and extrinsic mechanisms contribute to immune homeostasis, and in this issue of Seminars in Immunopathology, we will explore recent advances in our understanding of how the nervous system participates in immune homeostasis and how its dysregulation leads to inappropriate responses. Historically, the role of the nervous system in regulating immunity was marginalized until multiple neurotransmitter receptors were discovered to be expressed by immune cells, clearly indicating that the immune system responds to neural cues. Further proof of this interaction came with the description of sympathetic nerve fibers that innervate primary and secondary immune tissues, creating intimate interactions with immune cells. Here, we will explore some of those neuro-immune interactions that shape both the nature This article is a contribution to the special issue on Neuro-immune Interactions - Guest Editor: David Farrar * J. David Farrar [email protected] 1
Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA
and magnitude of the immune response as well as immune surveillance activities under homeostasis. Perhaps the most well-studied pathway of neurological control involves glucocorticoids, which have been used therapeutically for decades to treat inflammation and to mitigate the overwhelming cytokine storm that occurs in response to systemic infections. While expressed on many cells, the glucocorticoid receptor in immune cells, particularly innate cells, represents perhaps one of the most fundamental neuroimmune regulators that acutely blocks inflammatory cytokine secretion. Ikuta and colleagues provide an overview of glucocorticoids, the GC receptor, molecular interactions, and clinical interventions of this powerful primary immunomodulator [1]. Both sympathetic and parasympathetic neurotransmitters r
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