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00925njm 22002777a 4500 dc Herrero-Fernandez, Beatriz author Gómez Bris, Raquel author Ortega-Zapero, Marina author Saez, Angela author Iborra Martín, Salvador author Zorita, Virginia author Quintas, Ana author Vazquez, Enrique author Dopazo, Ana author Sánchez Madrid, Francisco author Arribas, Silvia Magdalena author González Granado, José María 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 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 10.1007/s00018-024-05423-9 https://hdl.handle.net/20.500.14352/108453 https://doi.org/10.1007/s00018-024-05423-9 https://link.springer.com/article/10.1007/s00018-024-05423-9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393282/ Role of Lamin A/C on dendritic cell function in antiviral immunity