Multiple neuropeptides in nerves supplying mammalian lymph nodes: messenger candidates for sensory and autonomic neuroimmunomodulation?☆
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3D anatomy of autonomic innervations in immune organs of a non-human primate and the human
2023, Fundamental ResearchControl of lymph node activity by direct local innervation
2022, Trends in NeurosciencesCitation Excerpt :Sympathetic fibers extend from the small plexuses associated with blood vessels into the subcapsular plexus and then branch in the parenchyma into the paracortical and cortical regions [23,30,34], where stromal and high endothelial cells, as well as T lymphocytes are present [1], while they avoid B cell follicles [21] (Figure 1). In line with this, staining for dopamine β-hydroxylase (DBH), which selectively marks NE-releasing fibers, and for the sympathetic co-transmitter neuropeptide Y (NPY) [26,35,36], is present in the perivascular plexus and is only rarely detected in the lymphoid parenchyma [32,36,37] (Figure 1). Retrograde tracing studies contributed substantially to understanding the innervation of LNs [37].
Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential
2021, CellCitation Excerpt :In many cases, nociceptor modulation of immunity involves bioactive neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P, which are released from activated peripheral terminals of nociceptors and act on various immune and stromal cells that express the corresponding receptors (Assas et al., 2014; Baral et al., 2019; Suvas, 2017). Peptidergic neurons of putative sensory origin innervate most, if not all, secondary lymphoid organs and barrier tissues, but their density, pattern of innervation, and neighboring cell types are notably different between tissues (Belvisi, 2002; Brierley et al., 2004; Felten et al., 1985; Fink and Weihe, 1988; Kurkowski et al., 1990; Oaklander and Siegel, 2005; Popper et al., 1988). This raises the intriguing possibility that sensory neurons targeting distinct peripheral sites may contribute differently to immune responses by engaging in local tissue-specific sensory neuro-immune circuits.
Germinal center formation, immunoglobulin production and hindlimb nociceptive sensitization after tibia fracture
2020, Brain, Behavior, and ImmunityCitation Excerpt :Importantly, neuropeptide (substance P and CGRP) signaling is required for neoantigen expression and pain-related IgM formation (Li et al., 2018). The innervation of lymph nodes by neuropeptide containing fibers is believed to be a pathway for neuro-immune signaling (Fink and Weihe, 1988; Huang et al., 2013). We also observed that sensitization after serum injection takes about one week to manifest indicating that sufficient accumulation of IgM at its pain-promoting target sites might take some time, and/or that secondary effector pathways such as the activation of complement may require time to reach the level where pain sensitivity is altered.
Interaction of neurotransmitters and neurochemicals with lymphocytes
2019, Journal of NeuroimmunologyCitation Excerpt :Studies so far have found only sympathetic innervation of the spleen (Felten et al., 1987; Felten and Olschowka, 1987; Nance and Sanders, 2007; Straub, 2004). (D) INNERVATION OF THE LYMPH NODES: SNS fibers enter the hilus of lymph nodes along with blood vessels, run along the vascular and lymphatic networks in the medulla, paracortex and cortical regions (Felten et al., 1984; Fink and Weihe, 1988), and branch into the T cell zones in the parenchyma of the medulla and paracortex (Novotny and Kliche, 1986). The SNS does not innervate the B cell-rich germinal centers (Felten et al., 1984; Sloan et al., 2007).
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Supported by the German Research Foundation, Stifterverband für die Deutsche Wissenschaft (Schering). Parts of this study have been reported at the Second World Congress of Neuroscience in Budapest (cf. 3) and are contained in the thesis of T. Fink.
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We thank N. Yanaihara (Japan) for the generous supply of VIP and PHI antiserum and A. Leibold for technical assistance.