Roles for TGF-β and Programmed Cell Death 1 Ligand 1 in Regulatory T Cell Expansion and Diabetes Suppression by Zymosan in Nonobese Diabetic Mice

被引:24
作者
Burton, Oliver T. [1 ]
Zaccone, Paola [1 ]
Phillips, Jenny M. [1 ]
De La Pena, Hugo [1 ,2 ]
Fehervari, Zoltan [1 ]
Azuma, Miyuki [3 ]
Gibbs, Sarah [1 ]
Stockinger, Brigitta [2 ]
Cooke, Anne [1 ]
机构
[1] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England
[2] Natl Inst Med Res, MRC, Dept Mol Immunol, London NW7 1AA, England
[3] Tokyo Med & Dent Univ, Dept Mol Immunol, Tokyo, Japan
基金
英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
PLASMACYTOID DENDRITIC CELLS; ANTIGEN-PRESENTING CELLS; NOD MICE; EXTRACELLULAR-MATRIX; RECEPTOR DECTIN-1; CANDIDA-ALBICANS; B-LYMPHOCYTES; IN-VIVO; INDUCTION; PREVENTS;
D O I
10.4049/jimmunol.1001365
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Zymosan is a complex fungal component shown to be capable of both promoting and suppressing the development of autoimmune disorders in mice. In this study, we show that a single injection of zymosan just prior to diabetes onset can significantly delay the progression of disease in NOD mice. Zymosan treatment of NOD mice induced the production of biologically active TGF-beta from cells infiltrating the pancreas and was associated with expansion of programmed cell death 1 ligand 1(+)TGF-beta(+) macrophages and Foxp3(+) regulatory T cells in vivo. Neutralization of either TGF-beta or programmed cell death 1 ligand 1 abrogated the protective effects of zymosan. Zymosan acted through TLR2 as well as ERK and p38 MAPK to induce macrophage secretion of TGF-beta and promotion of Foxp3(+) regulatory T cells in vitro and in vivo. The Journal of Immunology, 2010, 185: 2754-2762.
引用
收藏
页码:2754 / 2762
页数:9
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