2026-04-29T04:09:17Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/264062025-12-18T13:01:22Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Herrero-Fernández, Beatriz author Ortega-Zapero, Marina author Gómez-Bris, Raquel author Sáez, Angela author Iborra, Salvador author Zorita, Virginia author Quintas, Ana author Vázquez, Enrique author Dopazo, Ana author Sánchez-Madrid, Francisco author Arribas, Silvia Magdalena author González-Granado, Jose Maria author 2024-09-12 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. Cell Mol Life Sci. 2024 Sep 12;81(1):400. https://hdl.handle.net/20.500.12105/26406 39264480 Cellular and Molecular Life Sciences Vaccinia virus Dendritic cell Gene accessibility regulation Lamin A/C NFκB Viral immune response Role of lamin A/C on dendritic cell function in antiviral immunity.