کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2167396 1092327 2012 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Differential role of NF-κB, ERK1/2 and AP-1 in modulating the immunoregulatory functions of bone marrow-derived dendritic cells from NOD mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Differential role of NF-κB, ERK1/2 and AP-1 in modulating the immunoregulatory functions of bone marrow-derived dendritic cells from NOD mice
چکیده انگلیسی

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/DCs. 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-κB DNA binding complex contains p52 and p65 in GM/DCs, whereas it contains p52, p65 and RelB in IL-4/DCs. 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-κB pathways.


► DCs of NOD generated with GM-CSF (GM/DCs) are tolerogenic.
► GM/DCs induce better Treg conversion and expansion.
► GM/DCs produce high levels of IL-10 and very low amount of IL-12p70.
► ERK1/2 and AP-1 regulate IL-10 production but not in maturation resistance.
► IL-10 and IL-12 production are regulated by the nature of dimers in NF-κB complex.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Immunology - Volume 272, Issue 2, 2012, Pages 259–268
نویسندگان
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