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However, the precise mechanisms of this bi-directional crosstalk of the PNS and immune system remain mysterious. To study this kind of bi-directional crosstalk, we performed immunofluorescent staining of neurofilament and confocal microscopy to reveal the distribution of nerve fibers and nerve-immune cell associations inside mouse spleen. Our study demonstrates (i) extensive nerve fibers in all splenic compartments including the splenic nodules, periarteriolar lymphoid sheath, marginal zones, trabeculae, and red pulp; (ii) close associations of nerve fibers with blood vessels (including central arteries, marginal sinuses, penicillar arterioles, and splenic sinuses); (iii) close associations of nerve fibers with various subsets of dendritic cells, macrophages (Mac1<jats:sup>+<\/jats:sup> and F4\/80<jats:sup>+<\/jats:sup>), and lymphocytes (B cells, T helper cells, and cytotoxic T cells). Our data concerning the extensive splenic innervation and nerve-immune cell communication will enrich our knowledge of the mechanisms through which the PNS affects the cellular- and humoral-mediated immune responses in healthy and infectious\/non-infectious states.<\/jats:p>","DOI":"10.1038\/s41598-020-66619-0","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T10:05:07Z","timestamp":1592388307000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Distribution of nerve fibers and nerve-immune cell association in mouse spleen revealed by immunofluorescent staining"],"prefix":"10.1038","volume":"10","author":[{"given":"Dailun","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda A. 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