1. Expanding antigen-specific regulatory networks to treat autoimmunity.
- Author
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Clemente-Casares X, Blanco J, Ambalavanan P, Yamanouchi J, Singha S, Fandos C, Tsai S, Wang J, Garabatos N, Izquierdo C, Agrawal S, Keough MB, Yong VW, James E, Moore A, Yang Y, Stratmann T, Serra P, and Santamaria P
- Subjects
- Animals, Antigen-Presenting Cells immunology, B-Lymphocytes cytology, B-Lymphocytes immunology, CD11 Antigens immunology, Cell Differentiation, Cytokines immunology, Female, Histocompatibility Antigens Class II chemistry, Histocompatibility Antigens Class II genetics, Histocompatibility Antigens Class II immunology, Humans, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Transgenic, Nanomedicine, Nanoparticles chemistry, Nanoparticles therapeutic use, Organ Specificity, Prevalence, Solubility, T-Lymphocytes, Regulatory cytology, Autoantigens immunology, Autoimmunity immunology, T-Lymphocytes, Regulatory immunology
- 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.
- Published
- 2016
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