Molecular anatomy of the neuro-immune connection

Abstract

Light microscopic immunohistochemistry was employed to elucidate and compare the presence, distribution, and coexistence of various peptides, neuroendocrine markers and enzymes of the catecholamine pathway in nerves supplying lymphoid tissues in a variety of mammalian species. All lymphoid organs and tissues receive innervation by fibers containing dopamine-beta-hydroxylase and/or tyrosine hydroxylase, neural markers like protein gene product 9.5, synaptophysin and neurofilament and a varied spectrum of peptides. The prominent peptides were tachykinins (substance P, neurokinin A), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI). Opioid innervation was variable. Double immunofluorescence revealed coexistence of tachykinins and CGRP and of tyrosine hydroxylase and NPY. A minor proportion of fibers showed coexistence of NPY and tachykinins and of VIP/PHI and tachykinins. The possible importance of the complex peptidergic innervation of lymphoid tissues in inflammation, allergy, inflammatory pain and psycho-neuro-immuno-endocrine network function is discussed. A special immunomodulatory role of the sensory neurons is suggested.

Stimulation of Dopamine Receptor D5 Expressed on Dendritic Cells Potentiates Th17-Mediated Immunity

“…However, a number of more recent studies have shown that immune system cells can also be regulated by neurotransmitters (6)(7)(8)(9)(10)(11). Consistent with this, both primary and secondary lymphoid organs are highly innervated by sympathetic ends that store dopamine (DA) (12,13).…”

Dopamine Selectively Induces Migration and Homing of Naive CD8+ T Cells via Dopamine Receptor D3

“…The secondary lymphoid tissues are abundantly innervated by the sympathetic nerves that store a large amount of dopamine, and nerve fibers are particularly concentrated around vascular endothelial cells (7). The concentration of dopamine in the synapse is estimated to be 100 -300 M (24).…”

“…It is also known that CCR7 and CXCR4, via their respective chemokine ligands, play important roles in homing of naive T cells to the secondary lymphoid tissues (21,37,38). Furthermore, dopamine is present in the secondary lymphoid tissues at high levels (7,8). We therefore next examined a potential cooperation of chemokines and dopamine in induction of chemotaxis in human naive CD8 ϩ T cells.…”

“…Furthermore, both the primary and secondary lymphoid organs are highly innervated by the sympathetic nerves that store a large amount of dopamine (6,7). Lymphocytes are also capable of producing dopamine themselves (8).…”

Cloning of a novel putative G‐protein‐coupled receptor (NLR) which is expressed in neuronal and lymphatic tissue

“…Two independent clonal cell lines expressing the highest level of RC8 mRNA (data not shown) were tested for binding with the fol- The homology of the putative G-protein-coupled receptor NLR to both the cytokine and neuropeptide family of receptors raises the question of its biological importance in neuroimmune connections. Several neuropeptides, such as neuropeptide Y, calcitonin generelated peptide, galanin and opiods, besides their wide distribution throughout the central and peripheral nervous system, have been demonstrated to be localized in nerve endings innervating lymphoid organs [23]. Interestingly, neuropeptide Y-positive nerve terminals were found in close apposition with lymphoid compartments of the rat spleen [24].…”