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

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

Author information

1
Neuroscience Unit, University Hospital Center of Quebec - Laval University, Quebec City, Quebec, Canada.
2
Department of Microbiology and Immunology, Western University, London, Ontario, Canada.
3
Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
4
Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, Essen, Germany.
5
Infectious and Immune Disease Unit, University Hospital Center of Quebec - Laval University, Quebec City, Quebec, Canada.
6
Neuroimmunology Research Laboratory, University of Montreal Hospital Research Center, Montreal, Quebec, Canada.

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

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