ICAM1+ neutrophils promote chronic inflammation via ASPRV1 in B cell-dependent autoimmune encephalomyelitis

JCI Insight. 2017 Dec 7;2(23):e96882. doi: 10.1172/jci.insight.96882.

Abstract

Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive to date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental autoimmune encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated that neutrophils, once extravasated, acquire macrophage-like properties, including the potential for immunostimulation and MHC class II-mediated antigen presentation. In corroboration, super-resolution (3D stimulated emission-depletion [STED]) microscopy revealed neutrophils forming synapses with T and B cells in situ. Further, neutrophils specifically express the aspartic retroviral-like protease ASPRV1, which increases in the CNS during EAE and severe cases of multiple sclerosis. Without ASPRV1, mice immunized with a new B cell-dependent myelin antigen (but not with the traditional myelin oligodendrocyte glycoprotein peptide) develop a chronic phase of EAE that is less severe and even completely fades in many individuals. Therefore, ICAM1+ macrophage-like neutrophils can play both shared and nonredundant roles in autoimmune demyelination, among them perpetuating inflammation via ASPRV1.

Keywords: Autoimmune diseases; Autoimmunity; Demyelinating disorders; Neuroscience; Neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Aspartic Acid Endopeptidases / immunology*
  • B-Lymphocytes / immunology*
  • Chronic Disease
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Immunological Synapses / immunology
  • Immunophenotyping
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • Spinal Cord / immunology
  • T-Lymphocytes / immunology
  • Transcriptome / immunology

Substances

  • Icam1 protein, mouse
  • Taps protein, mouse
  • Intercellular Adhesion Molecule-1
  • Aspartic Acid Endopeptidases