Toribio-Fernandez, RaquelHerrero-Fernandez, BeatrizZorita, VirginiaLopez, Juan AntonioVazquez, JesusCriado, GabrielPablos, Jose LCollas, PhilippeSanchez-Madrid, FranciscoAndres, VicenteGonzalez-Granado, Jose Maria2020-01-142020-01-142019-12J Pathol. 2019; 249(4):509-220022-3417http://hdl.handle.net/20.500.12105/8879The mechanisms by which lamin A/C in CD4+ T-cells control intestinal homeostasis and can cause inflammatory bowel disease (IBD) are unknown. Here, we explore lamin A/C in a mouse model of IBD. Adoptive transfer to Rag1-/- mice of Lmna-/- CD4+ T-cells, which have enhanced regulatory T-cells (Treg) differentiation and function, induced less severe IBD than wild-type T-cells. Lamin A/C deficiency in CD4+ T-cells enhanced transcription of the Treg master regulator FOXP3, thus promoting Treg differentiation, and reduced Th1 polarization, due to epigenetic changes in the Th1 master regulator T-bet. In mesenteric lymph nodes, retinoic acid (RA) released by CD103+ dendritic cells downregulated lamin A/C in CD4+ T-cells, enhancing Treg differentiation. However, non-RA-producing CD103- dendritic cells predominated in peripheral lymph nodes, facilitating lamin A/C expression in CD4+ T-cells and therefore Th1 differentiation. Our findings establish lamin A/C as a key regulator of Th differentiation in physiological conditions and show it as a potential immune-regulatory target in IBD. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/CD4+ T-cellsFOXP3Inflammatory bowel diseaseLamin A/CRegulatory T-cellAttribution-NonCommercial-NoDerivatives 4.0 Internacional313729952494509-52210.1002/path.53321096-9896The Journal of pathologyopen access