AUTHOR=Casella Giacomo , Rasouli Javad , Thome Rodolfo , Descamps Hélène C. , Vattikonda Asrita , Ishikawa Larissa , Boehm Alexandra , Hwang Daniel , Zhang Weifeng , Xiao Dan , Park Jeongho , Zhang Guang-Xian , Alvarez Jorge I. , Rostami Abdolmohamad , Ciric Bogoljub 

TITLE=Interferon-γ/Interleukin-27 Axis Induces Programmed Death Ligand 1 Expression in Monocyte-Derived Dendritic Cells and Restores Immune Tolerance in Central Nervous System Autoimmunity

JOURNAL=Frontiers in Immunology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.576752

DOI=10.3389/fimmu.2020.576752

ISSN=1664-3224

ABSTRACT=Tolerance induction by intravenous (i.v.) injection of autoantigens has been explored for therapy of autoimmune diseases, including multiple sclerosis. However, because of the complexity of the immune system none of our current therapies have proved to be fully effective. Here, we describe a pathway whereby i.v.-injected autoantigen into mice with experimental autoimmune encephalomyelitis (EAE) induces IFN-γ secretion by CD4+ T cells, triggering IL-27 production by conventional dendritic cells type 1 (cDC1). IL-27 induces PD-L1 expression, via STAT3 activation, in monocyte-derived DCs (moDCs) infiltrated into the CNS of mice with EAE. PD-L1 interaction with PD-1 on pathogenic CD4+ T cells then promotes their apoptosis/anergy, resulting in disease amelioration. Our findings identify a key role of the IFN-γ/IL-27/PD-L1 axis, involving T cells/cDC1/moDCs in the induction of i.v. tolerance, which defines a pathway whereby autoantigen-induced IFN-γ secretion restores immune tolerance in CNS autoimmunity.