Yeste, AdaTakenaka, Maisa CMascanfroni, Ivan DNadeau, MeghanKenison, Jessica EPatel, BonnyTukpah, Ann-MarciaBabon, Jenny Aurielle BDeNicola, MeganKent, Sally CPozo, DavidQuintana, Francisco J2023-01-252023-01-252016-06-21http://hdl.handle.net/10668/10203Type 1 diabetes (T1D) is a T cell-dependent autoimmune disease that is characterized by the destruction of insulin-producing β cells in the pancreas. The administration to patients of ex vivo-differentiated FoxP3(+) regulatory T (Treg) cells or tolerogenic dendritic cells (DCs) that promote Treg cell differentiation is considered a potential therapy for T1D; however, cell-based therapies cannot be easily translated into clinical practice. We engineered nanoparticles (NPs) to deliver both a tolerogenic molecule, the aryl hydrocarbon receptor (AhR) ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), and the β cell antigen proinsulin (NPITE+Ins) to induce a tolerogenic phenotype in DCs and promote Treg cell generation in vivo. NPITE+Ins administration to 8-week-old nonobese diabetic mice suppressed autoimmune diabetes. NPITE+Ins induced a tolerogenic phenotype in DCs, which was characterized by a decreased ability to activate inflammatory effector T cells and was concomitant with the increased differentiation of FoxP3(+) Treg cells. The induction of a tolerogenic phenotype in DCs by NPs was mediated by the AhR-dependent induction of Socs2, which resulted in inhibition of nuclear factor κB activation and proinflammatory cytokine production (properties of tolerogenic DCs). Together, these data suggest that NPs constitute a potential tool to reestablish tolerance in T1D and potentially other autoimmune disorders.enAnimalsBasic Helix-Loop-Helix Transcription FactorsDiabetes Mellitus, Type 1HumansIndolesInsulin-Secreting CellsMice, Inbred NODNanoparticlesReceptors, Aryl HydrocarbonSuppressor of Cytokine Signaling ProteinsT-Lymphocytes, RegulatoryThiazolesresearch article2733018810.1126/scisignal.aad06121937-9145