RT Journal Article
T1 Role of Lamin A/C on dendritic cell function in antiviral immunity
A1 Herrero-Fernandez, Beatriz
A1 Gómez Bris, Raquel
A1 Ortega-Zapero, Marina
A1 Saez, Angela
A1 Iborra Martín, Salvador
A1 Zorita, Virginia
A1 Quintas, Ana
A1 Vazquez, Enrique
A1 Dopazo, Ana
A1 Sánchez Madrid, Francisco
A1 Arribas, Silvia Magdalena
A1 González Granado, José María
AB 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 NF-κB-dependent transcription. Furthermore, lamin A/C ablation modifies the gene accessibility 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 proposes some mechanisms through which lamin A/C may modulate DC function via gene accessibility and transcriptional regulation
PB Springer Nature
YR 2024
FD 2024-09-12
LK https://hdl.handle.net/20.500.14352/108453
UL https://hdl.handle.net/20.500.14352/108453
LA eng
NO Herrero-Fernández B, Ortega-Zapero M, Gómez-Bris R, et al. Role of lamin A/C on dendritic cell function in antiviral immunity. Cell Mol Life Sci. 2024;81(1):400. Published 2024 Sep 12. doi:10.1007/s00018-024-05423-9
NO Instituto de Salud Carlos III (ISCIII)
NO Ministerio de Ciencia, Innovación y Universidades (MCNU)
NO Universidad Francisco de Vitoria (UFV)
NO Comisión Europea
NO Comunidad de Madrid
NO La Caixa Health Research Grant
NO Ministerio de Economía y Competitividad
DS Docta Complutense
RD 8 abr 2025