1. Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2
- Author
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Bonny Patel, Jessica E. Kenison, Jenny Aurielle B. Babon, Sally C. Kent, Ada Yeste, Megan E DeNicola, David Pozo, Francisco J. Quintana, Ann-Marcia Tukpah, Maisa C. Takenaka, Meghan Nadeau, Ivan D. Mascanfroni, National Institutes of Health (US), Juvenile Diabetes Research Foundation, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, National Multiple Sclerosis Society (US), and Helmsley Charitable Trust
- Subjects
0301 basic medicine ,Indoles ,medicine.medical_treatment ,T cell ,Suppressor of Cytokine Signaling Proteins ,Biology ,Software_PROGRAMMINGTECHNIQUES ,medicine.disease_cause ,T-Lymphocytes, Regulatory ,Biochemistry ,Autoimmunity ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Mice, Inbred NOD ,Insulin-Secreting Cells ,Basic Helix-Loop-Helix Transcription Factors ,medicine ,Animals ,Humans ,Receptor ,Molecular Biology ,SOCS2 ,Type 1 diabetes ,Insulin ,Cell Biology ,medicine.disease ,Thiazoles ,Diabetes Mellitus, Type 1 ,030104 developmental biology ,medicine.anatomical_structure ,Receptors, Aryl Hydrocarbon ,Immunology ,Cancer research ,Nanoparticles ,Software_PROGRAMMINGLANGUAGES ,Ex vivo ,030215 immunology - Abstract
Yeste, Ada et al., 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 (T) cells or tolerogenic dendritic cells (DCs) that promote T 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 (NP) to induce a tolerogenic phenotype in DCs and promote T cell generation in vivo. NP administration to 8-week-old nonobese diabetic mice suppressed autoimmune diabetes. NP 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 T 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., This work was supported by grants ES025530, AI075285, and AI093903 from the NIH, 17-2011-371 from the Juvenile Diabetes Research Foundation, the Boston Area Diabetes Endocrinology Research Center (to F.J.Q.), and PI14-1600 from the Spanish Ministry of Economy and Competitiveness (ISCIII) with FEDER cofunding (to D.P.). M.C.T. received support from an educational grant from Mallinckrodt Pharmaceuticals (A113307) and from a postdoctoral fellowship (0571-15-6) from Coordination for the Improvement of Higher Education Personnel, Brazil. I.D.M. received support from an educational grant from Questcor (A219074) and from a postdoctoral fellowship (FG 2036-A1/1) from the National Multiple Sclerosis Society. S.C.K. received support from The Helmsley Charitable Trust.
- Published
- 2016