TLR2- and Dectin 1-associated innate immune response modulates T-cell response to pancreatic β-cell antigen and prevents type 1 diabetes.
TLR2- and Dectin 1-associated innate immune response modulates T-cell response to pancreatic β-cell antigen and prevents type 1 diabetes.
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作者：
Karumuthil-Melethil S;Sofi MH;Gudi R;Johnson BM;Perez N;Vasu C
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 β-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-β1, and IL-17. NOD mice that received β-cell-Ag–loaded, zymosan-exposed DCs showed delayed hyperglycemia. Injection of NOD mice at the prediabetic age and early hyperglycemic stage with β-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 β-cell-Ag and reversing early-stage hyperglycemia in T1D.
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影响因子：
4.4
作者：
Lin, Ming S.;Tse, Hubert M.;Delmastro, Meghan M.;Bertera, Suzanne;Wong, Caterina T.;Lakomy, Robert;He, Jing;Sklavos, Martha M.;Coudriet, Gina M.;Pietropaolo, Massimo;Trucco, Massimo M.;Piganelli, Jon D.
通讯作者：
Piganelli, Jon D.
影响因子：
7.7
作者：
Mi, QS;Ly, D;Delovitch, TL
通讯作者：
Delovitch, TL
影响因子：
4.4
作者：
Huang, XP;Zhu, JG;Yang, YP
通讯作者：
Yang, YP
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
15.9
作者：
Dillon, S;Agrawal, S;Pulendran, B
通讯作者：
Pulendran, B