Functional Circuitry of Neuro-Immune Communication in the Mesenteric Lymph Node and Spleen
30 Pages Posted: 6 May 2019 Sneak Peek Status: Review CompleteMore...
The peripheral nervous system is an active participant in immune responses capable of blocking aberrant activation of a variety of immune cells. As one of these neuro-immune circuits, the cholinergic anti-inflammatory pathway has been well established to reduce the severity of several immunopathologies. While the activation of this pathway by vagal nerve stimulation requires both sympathetic innervation of the spleen the neuro-immune circuitry remains highly controversial. Neuro-immune pathways in other lymphoid tissues such as mesenteric lymph nodes (MLN) that are critical to the surveillance of the small intestine and proximal colon have not been assessed. Using conditionally expressed Channelrhodopsin, selective stimulation of sympathetic post-ganglionic neurons in the superior mesenteric ganglion prevented LPS-induced TNFα production in the spleen and MLN but not the inguinal LN. Site selective stimulation of the SMG induced norepinephrine that resulted in β2 adrenergic receptors (β2AR) acetylcholine release in MLN and spleen. Using selective optogenetic blockade applied at the SMG, we determined that electrical VNS-evoked release of norepinephrine and acetylcholine in the MLN and spleen could be inhibited and restored LPS induced TNFα production. These studies identify the superior mesenteric ganglion as a critical node in the inhibition of immune function in the MLN and the spleen.
Keywords: Neuroimmunology, Cholinergic anti-inflammatory pathway, vagal nerve stimulation, peripheral optogenetics
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