期刊
CELLULAR IMMUNOLOGY
卷 272, 期 2, 页码 259-268出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2011.10.005
关键词
Dendritic cells; Tolerogenic; Type 1 diabetes; Cytokines
资金
- Canadian Institutes of Health Research (CIHR)
- Juvenile Diabetes Foundation International
- Diabetes Quebec
- Canadian Diabetes Association
- Fonds de la Recherche en Sante du Quebec
Tolerogenic dendritic cells represent a promising immunotherapy in autoimmunity. However, the molecular mechanisms that drive tolerogenic DCs functions are not well understood. We used GM-CSF or GM-CSF+IL-4 to generate tolerogenic (GM/DCs) and immunogenic (IL-4/DCs) BMDCs from NOD mice, respectively. GM/DCs were resistant to maturation, produced large amounts of IL-10 but not IL-12p70. GM/DCs displayed a reduced capacity to activate diabetogenic CD8(+) T-cells and were efficient to induce Tregs expansion and conversion. LPS stimulation triggered ERK1/2 activation that was sustained in GM/DCs but not in IL-4/DC5. ERK1/2 and AP-1 were involved in IL-10 production in GM/DCs but not in their resistance to maturation. Supershift analysis showed that NF-kappa B DNA binding complex contains p52 and p65 in GM/DCs, whereas it contains p52, p65 and RelB in IL-4/DC5. ChIP experiments revealed that p65 was recruited to IL-10 promoter following LPS stimulation of GM/DCs whereas its binding to IL-12p35 promoter was abolished. Our results suggest that immunoregulatory functions of GM/DCs are differentially regulated by ERK1/2, AP-1 and NF-kappa B pathways. (C) 2011 Elsevier Inc. All rights reserved.
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