Buckinx Roeland, Alpaerts Katrien, Pintelon Isabel, Cools Nathalie, Van Nassauw Luc, Adriaensen Dirk, Timmermans Jean-Pierre
Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
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.
Cell Tissue Res. 2017 Jun;368(3):459-467. doi: 10.1007/s00441-017-2578-z. Epub 2017 Feb 11.
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.
胃肠道持续暴露于从食物抗原到潜在致病生物体等大量抗原中，拥有哺乳动物体内最大的免疫细胞集合。这个免疫系统必须在引发积极免疫反应和维持耐受性之间保持微妙的平衡。胃肠道也是一个复杂的内在神经系统——肠神经系统（ENS）的所在地。各种神经-免疫通讯的体外研究表明，血管活性肠肽（VIP）作为一种重要的胃肠道神经递质，可调节单核吞噬细胞（MNP），即树突状细胞和巨噬细胞。我们采用逆转录加聚合酶链反应、免疫荧光、三维最大强度投影和免疫电子显微镜相结合的方法，研究回肠固有层（LP）中肠神经支配与MNP之间的相互作用。我们证明，ENS的VIP能纤维与CX3CR1 MNP相邻，并且VPAC1在小鼠LP的回肠CX3CR1 +细胞上组成性表达。我们还首次在超微结构水平上鉴定了LP中的CX3CR1免疫细胞。因此，我们的数据揭示了回肠LP中ENS与表达CX3CR1的免疫细胞之间VIP介导的神经-免疫相互作用所必需的分子成分的原位存在。
