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In situ proximity of CX3CR1-positive mononuclear phagocytes and VIP-ergic nerve fibers suggests VIP-ergic immunomodulation in the mouse ileum

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Abstract

Being continuously exposed to a plethora of antigens ranging from food antigens to potential pathogenic organisms, the gastrointestinal (GI) tract harbors the largest collection of immune cells in the mammalian body. This immune system has to maintain a delicate balance between mounting an active immune response and maintaining tolerance. The GI tract is also home to an elaborate intrinsic nervous system, the enteric nervous system (ENS). Various in vitro studies of neuro-immune communication have suggested that vasoactive intestinal peptide (VIP), an important GI neurotransmitter, modulates mononuclear phagocytes (MNPs), i.e., dendritic cells and macrophages. Using a combined approach of reverse transcription plus the polymerase chain reaction, immunofluorescence, three-dimensional maximum intensity projections and immunoelectron microscopy, we investigate the interaction between the enteric innervation and MNPs in the ileal lamina propria (LP). We demonstrate that VIP-ergic fibers of the ENS lie adjacent to CX3CR1+ MNPs and that VPAC1 is constitutively expressed on ileal CX3CR1+ cells in the LP of the mouse. We also identify, for the first time, CX3CR1+ immune cells in the LP at the ultrastructural level. Our data thus reveal the in situ presence of the molecular components that are necessary for a VIP-mediated neuro-immune interaction between the ENS and CX3CR1-expressing immune cells in the LP of the ileum.

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Acknowledgements

This study was funded by FWO-grant G019314N and BOF-GOA project 28313 of the University of Antwerp. The authors thank Elien Theuns, Carine Moers and Dominique De Rijck for their technical assistance.

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    Authors and Affiliations

    1. Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium

      Roeland Buckinx, Katrien Alpaerts, Isabel Pintelon, Dirk Adriaensen & Jean-Pierre Timmermans

    2. Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital (UZA), Edegem, Belgium

      Nathalie Cools

    3. Laboratory of Human Anatomy and Embryology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium

      Luc Van Nassauw

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    1. Roeland Buckinx
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    Correspondence to Jean-Pierre Timmermans.

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    Roeland Buckinx and Katrien Alpaerts contributed equally to this work.

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    Buckinx, R., Alpaerts, K., Pintelon, I. et al. In situ proximity of CX3CR1-positive mononuclear phagocytes and VIP-ergic nerve fibers suggests VIP-ergic immunomodulation in the mouse ileum. Cell Tissue Res 368, 459–467 (2017). https://doi.org/10.1007/s00441-017-2578-z

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