Experiment Overview
| Repository ID: | FR-FCM-Z4NS | Experiment name: | Coordinated glucocorticoid receptor and MAFB action induces tolerogenesis and epigenome remodelling in dendritic cells | MIFlowCyt score: | 50.37% |
| Primary researcher: | Octavio Morante-Palacios | PI/manager: | Esteban Ballestar | Uploaded by: | Octavio Morante-Palacios |
| Experiment dates: | 2021-11-12 - 2021-11-12 | Dataset uploaded: | Nov 2021 | Last updated: | Nov 2021 |
| Keywords: | [inflammation] [dendritic cells] [glucocorticoid receptor] [MAFB] [epigenetics] [tolerogenesis] | Manuscripts: | |||
| Organizations: |
Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, (Catalonia, Spain)
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| Purpose: | Glucocorticoids (GCs) exert potent anti-inflammatory effects in immune cells through the glucocorticoid receptor (GR). Dendritic cells (DCs), central actors for coordinating immune responses, acquire tolerogenic properties in response to GCs. Tolerogenic DCs (tolDCs) have emerged as a potential treatment for various inflammatory diseases. To date, the underlying cell type-specific regulatory mechanisms orchestrating GC-mediated acquisition of immunosuppressive properties remain poorly understood. In this study, we investigated the transcriptomic and epigenomic remodeling associated with differentiation to DCs in the presence of GCs. Our analysis demonstrates a major role of MAFB in this process, in synergy with GR. GR and MAFB both interact with methylcytosine dioxygenase TET2 and bind to genomic loci that undergo specific demethylation in tolDCs. We also show that the role of MAFB is more extensive, binding to thousands of genomic loci in tolDCs. Finally, MAFB knockdown erases the tolerogenic properties of tolDCs and reverts the specific DNA demethylation and gene upregulation. The preeminent role of MAFB is also demonstrated in vivo for myeloid cells from synovium in rheumatoid arthritis following GC treatment. Our results imply that, once directly activated by GR, MAFB plays a critical role in orchestrating the epigenomic and transcriptomic remodeling that define the tolerogenic phenotype. | ||||
| Conclusion: | Conclusions and detailed explanation regarding the methodology are explained in the manuscript. | ||||
| Comments: | None | ||||
| Funding: | We thank the CERCA Programme/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. E.B. was funded by the Spanish Ministry of Science and Innovation (MICINN; grant numbers SAF2017-88086-R & PID2020-117212RB-I00; AEI/FEDER, UE). O.M.-P. holds an i-PFIS PhD Fellowship (grant number IFI17/00034) from Acción Estratégica en Salud 2013-2016 ISCIII, co-financed by Fondo Social Europeo. C.O. and M.F.-B. were supported by the Swiss National Science Foundation (project 320030_176061). M.H. was supported by the Iten-Kohaut Foundation and the MLR foundation. | ||||
| Quality control: | MFIs are obtained by subtracting the negative control value to the value of each sample/channel. | ||||
