The goal of a therapy against autoimmune diseases would be to blunt immune responses against self antigens, without impairing systemic immunity. Our lab has been developing a nanoparticle-based therapy which consists of disease-relevant peptide-MHC complexes coated on iron-oxide nanoparticles (NPs). We have demonstrated that the therapeutic effects exerted by these NPs are associated with expansion of antigen-specific T-regulatory-type-1 (Tr1) cells and immuno-suppression of autoantigen-loaded antigen presenting cells (APCs) in an IL-10 and TGF-beta-dependent manner. We have established that suppression is disease- and organ-specific and effective in different autoimmune diseases (EAE and CIA) and genetic background (C57BL/6 and C57BL/10). We have found that NPs coated with epitopes released downstream from a disease-triggering insult can be as effective in suppressing disease as those coated with disease-inducing epitopes. EAE-relevant pMHC II-NPs were not only effective in suppressing inflammation but also in promoting re-myelination. Thus this therapy provides a negative feedback loop that serves to counter autoimmune disease progression.