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Sci Signal. 2016 Jun 21;9(433):ra61. doi: 10.1126/scisignal.aad0612.

Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2.

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Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01605, USA.
CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine (Consejo Superior de Investigaciones Científicas-University of Seville-Universidad Pablo de Olavide), Seville 41092, Spain. Department of Medical Biochemistry, Molecular Biology and Immunology, University of Seville Medical School, Seville 41009, Spain.
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.


Type 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.

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