Research ArticleImmunology

Tolerogenic nanoparticles inhibit T cell–mediated autoimmunity through SOCS2

Sci. Signal.  21 Jun 2016:
Vol. 9, Issue 433, pp. ra61
DOI: 10.1126/scisignal.aad0612

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Nanoparticles restore tolerance

Type 1 diabetes (T1D) is caused by the destruction of pancreatic β cells by inflammatory T cells. One strategy to treat T1D involves using suppressive T regulatory (Treg) cells that are grown in culture and then given back to patients to dampen the autoimmune response and induce tolerance. Yeste et al. used gold nanoparticles as a delivery mechanism to induce tolerance directly in a mouse model of T1D without having to grow immune cells ex vivo. The mice had increased numbers of Treg cells and decreased disease severity when given nanoparticles coated with an antigenic peptide of unprocessed insulin and a ligand that promotes the ability of dendritic cells to induce tolerance. These results suggest that nanoparticle-based therapies may be useful in restoring tolerance not only in T1D but also in other autoimmune diseases.

Abstract

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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