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oai:repisalud.isciii.es:20.500.12105/88792024-09-27T08:22:47Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Toribio-Fernandez, Raquel author Herrero-Fernandez, Beatriz author Zorita, Virginia author Lopez, Juan Antonio author Vazquez, Jesus author Criado, Gabriel author Pablos, Jose L author Collas, Philippe author Sanchez-Madrid, Francisco author Andres, Vicente author Gonzalez-Granado, Jose Maria author 2019-12 The 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. J Pathol. 2019; 249(4):509-22 10.1002/path.5332 1096-9896 0022-3417 The Journal of pathology 31372995 http://hdl.handle.net/20.500.12105/8879 CD4+ T-cells FOXP3 Inflammatory bowel disease Lamin A/C Regulatory T-cell Lamin A/C deficiency in CD4+ T-cells enhances regulatory T-cells and prevents inflammatory bowel disease