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The nervous system and the immune system communicate extensively with each other in order to maintain homeostasis and to regulate the immune response. The peripheral nervous system (PNS) communicates specifically with the immune system according to local interactions, including the “hardwiring” of sympathetic/parasympathetic (efferent) and sensory nerves (afferent) to lymphoid tissue and organs. To reveal this type of bidirectional neuroimmune interaction at the microscopic level, we used immunofluorescent staining of glial fibrillary acidic protein (GFAP) coupled with confocal microscopy/3D reconstruction to reveal the distribution of non-myelinating Schwann cells (NMSCs) and their interactions with immune cells inside mouse spleen. Our results demonstrate i) the presence of an extensive network of NMSC processes in all splenic compartments including the splenic nodules, periarteriolar lymphoid sheath (PALS), marginal zone, trabecula, and red pulp; ii) the close association of NMSC processes with blood vessels (including central artries and their branches, marginal sinuses, penicillar arterioles and splenic sinuses); iii) the close “synapse-like” interaction/association of NMSC processes with various subsets of dendritic cells (DCs; e.g ., CD4 + CD11c + DCs, B220 + CD11c + DCs, and F4/80 + CD11c + DCs), macrophages (F4/80 + ), and lymphocytes (B cells, CD4 + T helper cells). Our novel findings concerning the distribution of NMSCs and NMSC-leukocytes interactions inside mouse spleen should improve our understanding of the mechanisms through which the PNS affects cellular- and humoral-mediated immune responses in a variety of health conditions and infectious/non-infectious diseases.

The central nervous system (CNS) influences the immune system in a general fashion by regulating the systemic concentration of humoral substances, whereas the autonomic nervous system communicates specifically with the immune system according to local interactions. Data concerning the mechanisms of this bidirectional crosstalk of the peripheral nervous system (PNS) and immune system remain limited. To gain a better understanding of local interactions of the PNS and immune system, we have used immunofluorescent staining of glial fibrillary acidic protein (GFAP), coupled with confocal microscopy, to investigate the non-myelinating Schwann cell (NMSC)-immune cell interactions in mouse mesenteric lymph nodes. Our results demonstrate i) the presence of extensive NMSC processes and even of cell bodies in each compartment of the mouse mesenteric lymph node; ii) close associations/interactions of NMSC processes with blood vessels (including high endothelial venules) and the lymphatic vessel/sinus; iii) close contacts/associations of NMSC processes with various subsets of dendritic cells (such as CD4+CD11c+, CD8+CD11c+ dendritic cells), macrophages (F4/80+ and CD11b+ macrophages), and lymphocytes. Our novel findings concerning the distribution of NMSCs and NMSC-immune cell interactions inside the mouse lymph node should help to elucidate the mechanisms through which the PNS affects cellular- and humoral-mediated immune responses or vice versa in health and disease.