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TLR2- and Dectin 1-associated innate immune response modulates T-cell response to pancreatic ß-cell antigen and prevents type 1 diabetes.
Karumuthil-Melethil, Subha; Sofi, M Hanief; Gudi, Radhika; Johnson, Benjamin M; Perez, Nicolas; Vasu, Chenthamarakshan.
Afiliación
  • Karumuthil-Melethil S; Department of Surgery, University of Illinois at Chicago, Chicago, IL.
  • Sofi MH; Department of Microbiology and Immunology, College of Medicine, Medical University of South Carolina, Charleston, SC.
  • Gudi R; Department of Surgery, College of Medicine, Medical University of South Carolina, Charleston, SC.
  • Johnson BM; Department of Microbiology and Immunology, College of Medicine, Medical University of South Carolina, Charleston, SC.
  • Perez N; Department of Surgery, University of Illinois at Chicago, Chicago, IL.
  • Vasu C; Department of Microbiology and Immunology, College of Medicine, Medical University of South Carolina, Charleston, SC Department of Surgery, College of Medicine, Medical University of South Carolina, Charleston, SC vasu@musc.edu.
Diabetes ; 64(4): 1341-57, 2015 Apr.
Article en En | MEDLINE | ID: mdl-25377877
The progression of autoimmune diseases is dictated by deviations in the fine balance between proinflammatory versus regulatory responses, and pathogen recognition receptors (PRRs) play a key role in maintaining this balance. Previously, we have reported that ligation of Toll-like receptor 2 (TLR2) and Dectin 1 on antigen-presenting cells by zymosan results in a regulatory immune response that prevents type 1 diabetes (T1D). Here, we show that TLR2 and Dectin 1 engagement by zymosan promotes regulatory T-cell (Treg) responses against the pancreatic ß-cell-specific antigen (Ag). Unlike the TLR4 ligand, bacterial lipopolysaccharide, which induced proinflammatory cytokines and pathogenic T cells, zymosan induced a mixture of pro- and anti-inflammatory factors and Tregs, both in vitro and in vivo. Ag-specific T cells that are activated using zymosan-exposed dendritic cells (DCs) expressed Foxp3 and produced large amounts of IL-10, TGF-ß1, and IL-17. NOD mice that received ß-cell-Ag-loaded, zymosan-exposed DCs showed delayed hyperglycemia. Injection of NOD mice at the prediabetic age and early hyperglycemic stage with ß-cell-Ag, along with zymosan, results in a superior protection of the NOD mice from diabetes as compared with mice that received zymosan alone. This therapeutic effect was associated with increased frequencies of IL-10-, IL-17-, IL-4-, and Foxp3-positive T cells, especially in the pancreatic lymph nodes. These results show that zymosan can be used as an immune regulatory adjuvant for modulating the T-cell response to pancreatic ß-cell-Ag and reversing early-stage hyperglycemia in T1D.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Reguladores / Lectinas Tipo C / Diabetes Mellitus Tipo 1 / Células Secretoras de Insulina / Receptor Toll-Like 2 / Inmunidad Innata Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Diabetes Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Reguladores / Lectinas Tipo C / Diabetes Mellitus Tipo 1 / Células Secretoras de Insulina / Receptor Toll-Like 2 / Inmunidad Innata Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Diabetes Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos