Bibliographic Details
| Title: |
Role of the p38 MAPK/C/EBPβ Pathway in the Regulation of Phenotype and IL-10 and IL-12 Production by Tolerogenic Bone Marrow-Derived Dendritic Cells |
| Authors: |
Chantal Guindi, Alexandre Cloutier, Simon Gaudreau, Echarki Zerif, Patrick P. McDonald, Olga Tatsiy, Claude Asselin, Gilles Dupuis, Denis Gris, Abdelaziz Amrani |
| Source: |
Cells, Vol 7, Iss 12, p 256 (2018) |
| Publisher Information: |
MDPI AG, 2018. |
| Publication Year: |
2018 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
tolerogenic bone marrow-derived dendritic cells (BMDCs), CCAAT/enhancer-binding protein beta (C/EBPβ), Interleukins 10 and 12 (IL-10, IL-12), Cytology, QH573-671 |
| More Details: |
Dendritic cells (DCs) play a major role in innate and adaptive immunity and self-immune tolerance. Immunogenic versus tolerogenic DC functions are dictated by their levels of costimulatory molecules and their cytokine expression profile. The transcription factor C/EBPβ regulates the expression of several inflammatory genes in many cell types including macrophages. However, little is known regarding the role of C/EBPβ in tolerogenic versus immunogenic DCs functions. We have previously reported that bone marrow-derived DCs generated with GM-CSF (GM/DCs) acquire the signature of semi-mature tolerogenic IL-10-producing DCs as opposed to immunogenic DCs generated with GM-CSF and IL-4 (IL-4/DCs). Here, we show that tolerogenic GM/DCs exhibit higher levels of phosphorylation and enhanced DNA binding activity of C/EBPβ and CREB than immunogenic IL-4/DCs. We also show that the p38 MAPK/CREB axis and GSK3 play an important role in regulating C/EBPβ phosphorylation and DNA binding activity. Inhibition of p38 MAPK in GM/DCs resulted in a drastic decrease of C/EBPβ and CREB DNA binding activities, a reduction of their IL-10 production and an increase of their IL-12p70 production, a characteristic of immunogenic IL-4/DCs. We also present evidence that GSK3 inhibition in GM/DCs reduced C/EBPβ DNA binding activity and increased expression of costimulatory molecules in GM/DCs and their production of IL-10. Analysis of GM/DCs of C/EBPβ−/− mice showed that C/EBPβ was essential to maintain the semimature phenotype and the production of IL-10 as well as low CD4+ T cell proliferation. Our results highlight the importance of the p38MAPK-C/EBPβ pathway in regulating phenotype and function of tolerogenic GM/DCs. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2073-4409 |
| Relation: |
https://www.mdpi.com/2073-4409/7/12/256; https://doaj.org/toc/2073-4409 |
| DOI: |
10.3390/cells7120256 |
| Access URL: |
https://doaj.org/article/046d6f29846543559102859decdbd8b1 |
| Accession Number: |
edsdoj.046d6f29846543559102859decdbd8b1 |
| Database: |
Directory of Open Access Journals |
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