Journal
NATURE
Volume 530, Issue 7591, Pages 434-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature16962
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Funding
- Canadian Institutes of Health Research (CIHR)
- Diabetes Research Foundation
- Juvenile Diabetes Research Foundation (JDRF)
- Canadian Diabetes Association (CDA)
- Multiple Sclerosis Society of Canada (MSSC)
- Brawn Family Foundation
- National Research Council of Canada-Industrial Research Assistance Program (NRC-IRAP)
- Instituto de Investigaciones Sanitarias Carlos III (ISCIII) Integrated Project of Excellence
- Instituto de Investigaciones Sanitarias Carlos III (ISCIII) Integrated Project of FEDER
- Ministerio de Economia y Competitividad of Spain (MINECO)
- European Association for the study of diabetes (EASD)
- Sarda Farriol Research Programme
- European Community
- AXA Research Fund
- endMS network
- Rio Hortega fellowship
- Spanish Society for Diabetes
- Alberta Heritage Foundation of Medical Research (AHFMR)
- CDA
- JDRF Career Development Award
- Diabetes Association (Foothills)
- Alberta Innovates [201200614, 201300669] Funding Source: researchfish
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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 (T(R)1)-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 T(R)1-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.
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