Neural circuitry and immunity
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NEUROIMMUNOLOGY
Neural circuitry and immunity Valentin A. Pavlov1 • Kevin J. Tracey1
Ó Springer Science+Business Media New York 2015
Valentin A. Pavlov
Abstract Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuro-immune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex, are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases define the emerging field of Bioelectronic Medicine. Keywords
Neurons Immunity Inflammation Vagus nerve Cytokines Cholinergic
Introduction The more we know about the molecular mechanisms of a disease, the better therapeutic approaches we can design to treat and potentially cure it. This is one of the main principles of clinically oriented research, which has led to successful treatments of many disorders. Still, there are numerous diseases with no adequate treatments despite serious research efforts, employing state-of-the-art technology, to identify new molecular therapeutic targets. There are several reasons for this failure to successfully translate research discoveries into the clinic, including the complexity of mechanisms regulating these targets within
& Valentin A. Pavlov [email protected] Kevin J. Tracey [email protected] 1
Center for Biomedical Science, The Feinstein Institute for Medical Research, 350 Community Dr, Manhasset, NY 11030, USA
the scope of major biological events and the alteration and dysfunction of these regulatory mechanisms in disease settings. While this may sound trivial to many, and the need for new multidisciplinary approaches seems obvious, the path forward is not always clear. Here we outline important aspects of research performed at the crossroads between neuroscience and immunology, which hold a great promise to significantly advance the treatment of a broad spectrum of diseases characterized by immune dysfunction. This work has provided important insight into the role of neurons as partners of immune cells in the regulation of inflammation, which has significant implications in disease pathogenesis. It has now become clear that neurons sense inflammatory products and that neuronal activity is modulated in inflammatory conditions. Moreover, neurons can detect molecules associated with pathogen invasion simultaneously with, or even before, immune cells [1]. The nervou
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