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Cell Immunol. 2012;272(2):259-68. doi: 10.1016/j.cellimm.2011.10.005. Epub 2011 Oct 15.

Differential role of NF-κB, ERK1/2 and AP-1 in modulating the immunoregulatory functions of bone marrow-derived dendritic cells from NOD mice.

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  • 1Immunology Division, and Centre de Recherche Clinique Etienne LeBel, University of Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.

Abstract

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
22070873
[PubMed - indexed for MEDLINE]
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