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

J Autoimmun. 2024 Sep:148:103292. doi: 10.1016/j.jaut.2024.103292. Epub 2024 Jul 26.

Abstract

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, the experimental autoimmune encephalomyelitis (EAE). Breakdown of epithelial barriers increases intestinal permeability and systemic dissemination of microbiota-derived molecules. However, whether the 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, leading to vascular remodeling and expansion of intestinal villi capillary bed during disease symptomatic phase in 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 marker lymphatic 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 to mitigate 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.

Keywords: Angiogenesis; B cell; Experimental autoimmune encephalomyelitis; Gut-brain axis; Gut–vascular barrier; Neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis
  • Animals
  • B-Lymphocytes* / immunology
  • B-Lymphocytes* / metabolism
  • Brain-Gut Axis / immunology
  • Cell Proliferation
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental* / immunology
  • Encephalomyelitis, Autoimmune, Experimental* / metabolism
  • Encephalomyelitis, Autoimmune, Experimental* / pathology
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Female
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestines / blood supply
  • Intestines / immunology
  • Intestines / pathology
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology
  • Neovascularization, Pathologic / immunology
  • Neuroinflammatory Diseases / etiology
  • Neuroinflammatory Diseases / immunology
  • Neuroinflammatory Diseases / metabolism
  • Neuroinflammatory Diseases / pathology