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In this study, we investigated how NE release and \u03b12-adrenergic receptor (\u03b12AR) modulation influence neuroimmune interactions in the spleen and mesenteric lymph nodes (MLNs), 2 secondary lymphoid tissues with distinct innervation patterns. Using fast-scan cyclic voltammetry (FSCV), we found that the spleen exhibited more frequent and higher-amplitude NE events than the MLNs, consistent with its denser sympathetic innervation. Pharmacological manipulation of \u03b12ARs revealed that yohimbine hydrochloride, an \u03b12AR antagonist, increased NE release in both organs, while dexmedetomidine hydrochloride, an \u03b12AR agonist, suppressed it, often below detection thresholds. Complementary 3D immunohistochemistry demonstrated tissue- and cell type\u2013specific changes in immune cell proximity to neuronal structures following adrenergic modulation, with T cells and B cells displaying distinct spatial reorganization. These findings highlight that \u03b12AR signaling fine-tunes NE release and immune cell localization in a context-dependent manner, influenced by organ-specific architecture and innervation. Our results underscore the importance of dynamic local neuroimmune interactions in immune regulation and suggest potential therapeutic opportunities for targeting adrenergic signaling in inflammatory and autoimmune diseases.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf306","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:48:02Z","timestamp":1762861682000},"source":"Crossref","is-referenced-by-count":1,"title":["\u03b12-Adrenergic modulation of neuroimmune interactions differs between the spleen and mesenteric lymph nodes"],"prefix":"10.1093","volume":"215","author":[{"given":"Alexandra K","family":"Brooke","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Cincinnati , Cincinnati, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P","family":"Murrow","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cincinnati , Cincinnati, 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