RT Journal Article
SR Electronic
T1 Targeting MOG to skin macrophages prevents EAE in macaques through TGFβ-induced peripheral tolerance
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 571828
DO 10.1101/571828
A1 Claire-Maëlle Fovet
A1 Lev Stimmer
A1 Vanessa Contreras
A1 Philippe Horellou
A1 Audrey Hubert
A1 Nabila Sediki
A1 Catherine Chapon
A1 Sabine Tricot
A1 Carole Leroy
A1 Julien Flament
A1 Julie Massonneau
A1 Nicolas Tchitchek
A1 Bert A. ’t Hart
A1 Sandra Zurawski
A1 Peter Klucar
A1 Kumaran Deiva
A1 Gerard Zurawski
A1 SangKon Oh
A1 Roger Le Grand
A1 Ché Serguera
YR 2019
UL http://biorxiv.org/content/early/2019/03/09/571828.abstract
AB To study the effect of vaccination on tolerization to the myelin antigen MOG we used a macaque model of experimental autoimmune encephalitis (EAE) in which immunization with recombinant human myelin oligodendrocyte glycoprotein (rhMOG) elicits brain inflammation and demyelination mediated by MOG-specific autoreactive CD4+ T lymphocytes and anti-MOG IgG. For antigen targeting to tolerizing antigen presenting cells, we used a recombinant antibody directed to the Dendritic Cells (DC)-Asialoglycoprotein receptor (DC-ASGPR). The intradermal administration of an anti-DC-ASGPR-MOG fusion protein, but not a control anti-DC-ASGPR-PSA (prostate specific antigen) protein, protected monkeys committed to develop EAE. Although effective treatment did not modify anti-MOG IgG production, it prevented the CD4+ T lymphocyte activation and pro-inflammatory cytokine production. Moreover, animals treated with anti-DC-ASGPR-MOG experienced a rise of MOG-specific CD4+CD25+FOXP3+CD39+ regulatory T cells as well as a TGFβ1, TGFβ2 and IL-8 upsurge after rhMOG re-immunization. Our results indicate that the pathogenicity of autoantibodies directed to MOG is mitigated in the presence of MOG-specific regulatory lymphocytes. This vaccination scheme appears suitable to treat relapsing autoimmune diseases with identified autoantigens such as that harboring anti-MOG or anti-AQP4 autoantibodies.