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Functional Circuitry of Neuro-Immune Communication in the Mesenteric Lymph Node and Spleen

30 Pages Posted: 6 May 2019 Publication Status: Review Complete

See all articles by Kaitlin Murray

Kaitlin Murray

University of California, Davis - Department. of Anatomy, Physiology, and Cell Biology

Mariana Barboza Gardner

University of California, Davis - Department. of Anatomy, Physiology, and Cell Biology

Kavi M. Rude

University of California, Davis - Department. of Anatomy, Physiology, and Cell Biology

Ingrid Brust-Mascher

University of California, Davis - Department. of Anatomy, Physiology, and Cell Biology

Colin Reardon

University of California, Davis - Department. of Anatomy, Physiology, and Cell Biology

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Abstract

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

Suggested Citation

Murray, Kaitlin and Barboza Gardner, Mariana and Rude, Kavi M. and Brust-Mascher, Ingrid and Reardon, Colin, Functional Circuitry of Neuro-Immune Communication in the Mesenteric Lymph Node and Spleen (May 3, 2019). Available at SSRN: https://ssrn.com/abstract=3381955 or http://dx.doi.org/10.2139/ssrn.3381955
This version of the paper has not been formally peer reviewed.

Kaitlin Murray

University of California, Davis - Department. of Anatomy, Physiology, and Cell Biology

United States

Mariana Barboza Gardner

University of California, Davis - Department. of Anatomy, Physiology, and Cell Biology

United States

Kavi M. Rude

University of California, Davis - Department. of Anatomy, Physiology, and Cell Biology

United States

Ingrid Brust-Mascher

University of California, Davis - Department. of Anatomy, Physiology, and Cell Biology ( email )

United States

Colin Reardon (Contact Author)

University of California, Davis - Department. of Anatomy, Physiology, and Cell Biology ( email )

United States

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