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Role of Lamin A/C on dendritic cell function in antiviral immunity Herrero-Fernandez, Beatriz Gómez Bris, Raquel Ortega-Zapero, Marina Saez, Angela Iborra Martín, Salvador Zorita, Virginia Quintas, Ana Vazquez, Enrique Dopazo, Ana Sánchez Madrid, Francisco Arribas, Silvia Magdalena González Granado, José María 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 2024-09-30T07:09:33Z 2024-09-30T07:09:33Z 2024-09-30T07:09:33Z 2024-09-12 journal article https://hdl.handle.net/20.500.14352/108453 XXXX-XXXX 10.1007/s00018-024-05423-9 eng info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00306/ES/INMUNOLOGIA, INMUNOPATOLOGIA Y TERAPIA EN ENFERMEDAD INFLAMATORIA INTESTINAL/ info:eu-repo/grantAgreement/MCNU/PID2021/125415OB-I00 info:eu-repo/grantAgreement/MCNU/PID-2020/120412RB-I00 info:eu-repo/grantAgreement/CHRG/LCF/PR/ HR23/52430018 info:eu-repo/grantAgreement/MCNU/FPU18/00895 info:eu-repo/grantAgreement/ISCII/PI24/00146 info:eu-repo/grantAgreement/MCNU/PEJ-2020-TL/BMD- 17604 info:eu-repo/grantAgreement/CAM/LCF/PR/ HR23/52430018 info:eu-repo/grantAgreement/MCNU/FPU19/01774 info:eu-repo/grantAgreement/ISCII/PI20/00306 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 http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 International Springer Nature