Functional circuitry of neuro-immune communication in the mesenteric lymph node and spleen

Murray, Kaitlin; Barboza, Mariana; Rude, Kavi M.; Brust‐Mascher, Ingrid; Reardon, Colin

doi:10.1016/j.bbi.2019.08.188

Cited by 43 publications

(40 citation statements)

References 59 publications

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“…Electrodes were implanted in the T‐cell zone because of evidence that this region contains sympathetic neural innervation. (Felten & Felten, 1988; Felten et al., 1984; Murray et al., 2019). Within approximately 1–2 min after implantation, spontaneous catecholamine events were detected.…”

Section: Resultsmentioning

confidence: 99%

“…Sympathetic neurons innervate immune organs of the gastrointestinal tract including the mesenteric lymph nodes (MLN) (Murray, Barboza, Rude, Brust‐Mascher, & Reardon, 2019; Wülfing & Günther, 2015; Wülfing, Schuran, Urban, Oehlmann, & Günther, 2018) and Peyer's patches (Bhalla, Murakami, & Owen, 1981) to provide a direct pathway for neuroimmune communication. Sympathetic neurons release norepinephrine (NE) (Livnat, Felten, Carlson, Bellinger, & Felten, 1985; Madden et al 1995; Murray et al., 2019), ATP (Patel, Rogers, Wieder, O’Hare, & Boutelle, 2011), and neuropeptide Y (Mitić, Stanojević, Kuštrimović, Vujić, & Dimitrijević, 2011; Nordlind, Mutt, & Sundström, 1988) to act as immunomodulators. NE has been shown to be of particular importance in immunomodulation (Livnat et al., 1985).…”

Section: Introductionmentioning

confidence: 99%

“…Lymph nodes are spatially complex organs with a sophisticated network of signals that regulate immune responses (Felten & Felten, 1988; Murray et al., 2019; Wülfing & Günther, 2015; Wülfing et al., 2018). The MLN’s are the hubs of the immune system in the gut and therefore, an attractive site to study neuroimmune communication (Santiago et al., 2008; Buettner et al 2012).…”

Section: Introductionmentioning

confidence: 99%

“…These medullary cords are intertwined with noradrenergic (NA) sympathetic nerve fibers that extend deeper into the MLN (Park, Galligan, Fink, & Swain, 2006). NA nerve fibers innervate from the medulla to the T‐cell zone and to the edges of the cortex (Felten & Felten, 1988; Hu et al., 2019; Murray et al., 2019; Popper, Mantyh, Vigna, Maggio, & Mantyh, 1988; Shi et al., 2017; Wülfing & Günther, 2015; Wülfing et al., 2018). The cortex is where B‐cells are packaged in follicles and the site of entrance for transient antigen presenting cells (APC) through the afferent lymphatics (Gretz, Anderson, & Shaw, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…In this study, FSCV is used to monitor rapid spontaneous catecholamine signaling in MLN slices ex vivo. The use of carbon‐fiber microelectrodes allows precise positioning within the T‐cell zone where noradrenergic sympathetic projections are prevalent (Murray et al., 2019; Wülfing & Günther, 2015; Wülfing et al., 2018). Rapid unstimulated release was observed in the T‐cell zone with an average of 2.9 ± 0.43 transients per minute ( n = 23).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Subsecond spontaneous catecholamine release in mesenteric lymph node ex vivo

Lim

Regan

Ross

2020

Journal of Neurochemistry

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Measuring the dynamics of neurochemical‐regulated immunity, particularly in the gut, has been a growing interest over the last several years because of its important implications in gastrointestinal inflammation, neurodegeneration, and even depression. Sympathetic noradrenergic nerves innervate the gastrointestinal tract and resident immune organs, including the mesenteric lymph nodes (MLN) and Peyer's patches. Previous research has suggested that neuronal inputs in the MLN release norepinephrine (NE) at neural‐immune synapses to regulate immune function. The current immunological techniques do not have the appropriate temporal or spatial resolution to monitor this dynamic process in real‐time, within specific regions of intact lymphoid organs. Monitoring dynamic neural signaling within intact immune organs, in real‐time, would facilitate a deeper understanding of neuroimmune communication and would allow the mechanism of rapid immunomodulation to be elucidated. Here, we overcome this technological barrier by coupling real‐time neurochemical detection using fast‐scan cyclic voltammetry (FSCV) in live MLN slices from C57BL/6 mice. We have discovered rapid, spontaneous catecholamine transients in the T‐cell zone of the MLN which are on the order of a few hundred nanomolar, rapid (a few seconds), and frequent (every 20‐s). We demonstrate that the β2‐adrenergic receptor and the classic catecholamine transporters (DAT and NET) play a minor role in transient regulation in the MLN suggesting that regulation at the neural‐immune synapse is quite complicated and further mechanistic studies are needed. Overall, these findings provide direct evidence for rapid neurochemical events in the MLN which could have a major impact on our understanding of neurochemical‐regulated immunomodulation in the gut.

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Section: Resultsmentioning

confidence: 99%