Molecular anatomy of the neuro-immune connection

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.