Please use this identifier to cite or link to this item:
Title: Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2.
Authors: Yeste, Ada
Takenaka, Maisa C
Mascanfroni, Ivan D
Nadeau, Meghan
Kenison, Jessica E
Patel, Bonny
Tukpah, Ann-Marcia
Babon, Jenny Aurielle B
DeNicola, Megan
Kent, Sally C
Pozo, David
Quintana, Francisco J
metadata.dc.subject.mesh: Animals
Basic Helix-Loop-Helix Transcription Factors
Diabetes Mellitus, Type 1
Insulin-Secreting Cells
Mice, Inbred NOD
Receptors, Aryl Hydrocarbon
Suppressor of Cytokine Signaling Proteins
T-Lymphocytes, Regulatory
Issue Date: 21-Jun-2016
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.
metadata.dc.identifier.doi: 10.1126/scisignal.aad0612
Appears in Collections:Producción 2020

Files in This Item:
There are no files associated with this item.

This item is protected by original copyright

Except where otherwise noted, Items on the Andalusian Health Repository site are licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives License.