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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 18, 2024 |
| Title |
Role of Lamin A/C on dendritic cell function in antiviral immunity |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Dendritic cells (DCs) play a crucial role in orchestrating immune responses, particularly in promoting IFNγ-producing-CD8 cytotoxic T lymphocytes (CTLs) and IFNγ-producing -CD4 T helper 1 (Th1) cells, which are essential for defending against viral infections. Additionally, the nuclear envelope protein lamin A/C has been implicated in T cell immunity. Nevertheless, the intricate interplay between innate and adaptive immunity in response to viral infections, particularly the role of lamin A/C in DC functions within this context, remains poorly understood. In this study, we demonstrate that mice lacking lamin A/C in myeloid LysM promoter-expressing cells exhibit a reduced capacity to induce Th1 and CD8 CTL responses, leading to impaired clearance of acute primary Vaccinia virus (VACV) infection. Remarkably, in vitro-generated granulocyte macrophage colony-stimulating factor bone marrow-derived DCs (GM-CSF BMDCs) show high levels of lamin A/C. Lamin A/C absence on GM-CSF BMDCs does not affect the expression of costimulatory molecules on the cell membrane but it reduces the cellular ability to form immunological synapses with naïve CD4 T cells. Lamin A/C deletion induces alterations in NFκB nuclear localization, thereby influencing NFκB-dependent transcription. Furthermore, lamin A/C ablation modifies the epigenetic signature of BMDCs, predisposing these cells to mount a less effective antiviral response upon TLR stimulation. This study highlights the critical role of DCs in interacting with CD4 T cells during antiviral responses and elucidates the molecular mechanisms through which lamin A/C modulates DC function via epigenetic and transcriptional regulation.
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| Overall design |
We performed ATAC sequencing using BMDCs of WT and Lmna-/- mice. Samples are processed in biological duplicates, all 4 samples processed in paralel to avoid technical bias. For the peak identification all peaks included in both replicates of each condition are used.
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| Contributor(s) |
Herrero-Fernandez B, Gómez Bris R, Ortega Zapero M, Saez A, Iborra S, Zorita V, Quintas A, Vazquez E, Dopazo A, Sánchez-Madrid F, Magdalena Arribas S, Gonzalez Granado JM |
| Citation(s) |
39264480 |
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| Submission date |
Jun 11, 2024 |
| Last update date |
Sep 19, 2024 |
| Contact name |
Enrique Vazquez de Luis |
| E-mail(s) |
quiquevzquez@gmail.com
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| Organization name |
CNIC
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| Lab |
Genomics Unit
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| Street address |
Melchor Fernandez Almagro, 3
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| City |
Madrid |
| State/province |
Madrid |
| ZIP/Postal code |
28029 |
| Country |
Spain |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1122695 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE269613_AllPeaks.peak.txt.gz |
525.9 Kb |
(ftp)(http) |
TXT |
| GSE269613_RAW.tar |
561.5 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
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