Logo image
Back
Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity
Journal article   Open access   Peer reviewed

Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity

Divya Sagar, Narendra P Singh, Rashida Ginwala, Xiaofang Huang, Ramila Philip, Mitzi Nagarkatti, Prakash Nagarkatti, Konstantin Neumann, Jürgen Ruland, Allison M Andrews, …
Scientific reports, v 7(1), 2707
02 Jun 2017
DOI: https://doi.org/10.1038/s41598-017-03027-x
PMID: 28578388
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1038/s41598-017-03027-xView
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Animals Antibodies, Blocking - pharmacology Central Nervous System - immunology Central Nervous System - metabolism Central Nervous System - pathology Chemokine CCL2 - metabolism Dendritic Cells - drug effects Dendritic Cells - immunology Dendritic Cells - metabolism Encephalomyelitis, Autoimmune, Experimental - diagnosis Encephalomyelitis, Autoimmune, Experimental - drug therapy Encephalomyelitis, Autoimmune, Experimental - etiology Encephalomyelitis, Autoimmune, Experimental - metabolism Endothelium, Vascular - metabolism Immunity - drug effects Immunity - genetics Lectins - genetics Lectins - metabolism Lectins, C-Type - antagonists & inhibitors Lectins, C-Type - genetics Lectins, C-Type - metabolism Mice Mice, Knockout Models, Biological Myeloid Cells - drug effects Myeloid Cells - immunology Myeloid Cells - metabolism Phenotype Protein Binding Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism Protein Tyrosine Phosphatase, Non-Receptor Type 6 - metabolism Receptors, Mitogen - antagonists & inhibitors Receptors, Mitogen - genetics Recurrence Severity of Illness Index Signal Transduction Transendothelial and Transepithelial Migration
The mechanism of dendritic cells (DCs) recruitment across the blood brain barrier (BBB) during neuroinflammation has been the least explored amongst all leukocytes. For cells of myeloid origin, while integrins function at the level of adhesion, the importance of lectins remains unknown. Here, we identified functions of one C-type lectin receptor, CLEC12A, in facilitating DC binding and transmigration across the BBB in response to CCL2 chemotaxis. To test function of CLEC12A in an animal model of multiple sclerosis (MS), we administered blocking antibody to CLEC12A that significantly ameliorated disease scores in MOG -induced progressive, as well as PLP -induced relapsing-remitting experimental autoimmune encephalomyelitis (EAE) mice. The decline in both progression and relapse of EAE occurred as a result of reduced demyelination and myeloid cell infiltration into the CNS tissue. DC numbers were restored in the spleen of C57BL/6 and peripheral blood of SJL/J mice along with a decreased TH17 phenotype within CD4 T-cells. The effects of CLEC12A blocking were further validated using CLEC12A knockout (KO) animals wherein EAE disease induction was delayed and reduced disease severity was observed. These studies reveal the utility of a DC-specific mechanism in designing new therapeutics for MS.

Metrics

15 Record Views
34 citations in Web of Science
37 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
Logo image