Expanding antigen-specific regulatory networks to treat autoimmunity.

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.