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Nature. 2016 Feb 25;530(7591):434-40. doi: 10.1038/nature16962. Epub 2016 Feb 17.

Expanding antigen-specific regulatory networks to treat autoimmunity.

Author information

1
Julia McFarlane Diabetes Research Centre (JMDRC), and Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
2
Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, 08036, Spain.
3
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain.
4
Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain.
5
Hotchkiss Brain Institute and Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
6
Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101-2795, USA.
7
Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
8
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

Abstract

Regulatory T cells hold promise as targets for therapeutic intervention in autoimmunity, but approaches capable of expanding antigen-specific regulatory T cells in vivo are currently not available. Here we show that systemic delivery of nanoparticles coated with autoimmune-disease-relevant peptides bound to major histocompatibility complex class II (pMHCII) molecules triggers the generation and expansion of antigen-specific regulatory CD4(+) T cell type 1 (TR1)-like cells in different mouse models, including mice humanized with lymphocytes from patients, leading to resolution of established autoimmune phenomena. Ten pMHCII-based nanomedicines show similar biological effects, regardless of genetic background, prevalence of the cognate T-cell population or MHC restriction. These nanomedicines promote the differentiation of disease-primed autoreactive T cells into TR1-like cells, which in turn suppress autoantigen-loaded antigen-presenting cells and drive the differentiation of cognate B cells into disease-suppressing regulatory B cells, without compromising systemic immunity. pMHCII-based nanomedicines thus represent a new class of drugs, potentially useful for treating a broad spectrum of autoimmune conditions in a disease-specific manner.

PMID:
26886799
DOI:
10.1038/nature16962
[Indexed for MEDLINE]

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