Perivascular B cells link intestinal angiogenesis to immunity and to the gut-brain axis during neuroinflammation

Disruption of gut barrier function and intestinal immune cell homeostasis are increasingly considered critical players in pathogenesis of extra-intestinal inflammatory diseases, including multiple sclerosis (MS) and its prototypical animal model, theexperimental autoimmune encephalomyelitis (EAE). Breakdown of epithelial barriers increases intestinal permeability and systemic dissemination of microbiota-derived molecules. However,whetherthe gut-vascular barrier (GVB) is altered during EAE has not been reported. Here, we demonstrate that endothelial cell proliferation and vessel permeability increase before EAE clinical onset, leadingto vascular remodelingand expansion of intestinal villi capillary bed during disease symptomatic phasein an antigen-independent manner. Concomitant to onset of angiogenesis observed prior to neurological symptoms, we identify an increase of intestinal perivascular immune cells characterized by the surface markerlymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE-1). LYVE-1+is expressed more frequently on B cells that show high levels of CD73 and have proangiogenic properties. B cell depletion was sufficient tomitigate enteric blood endothelial cell proliferation following immunization for EAE. In conclusion, we propose that altered intestinal vasculature driven by a specialized LYVE-1+B cell subset promotes angiogenesis and that loss of GVB function is implicated in EAE development and autoimmunity. Overall design: Comparative gene expression profiling analysis of RNA-seq data for small intestinal (jejunum section) B lymphocytes isolated from mice immunized for experimental autoimmune encephalomyelitis (EAE) at 7 days post-immunization (DPI) depending on their expression of the surface marker lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE-1). Intestinal B cells were FACS sorted as viable CD45+ CD11b- F4/80- CD11c- B220+ LYVE-1+ and viable CD45+ CD11b- F4/80- CD11c- B220+ LYVE-1- from 6 mice.