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.

中文翻译：

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CD4 + T细胞中Lamin A / C缺乏症可增强调节性T细胞并预防炎症性肠病。

CD4 + T细胞中层粘连蛋白A / C控制肠道稳态并可能引起炎性肠病（IBD）的机制尚不清楚。在这里，我们探索了IBD小鼠模型中的lamin A / C。具有增强的调节性T细胞（Treg）分化和功能的Lmna-/-CD4 + T细胞向Rag1-/-小鼠的过继转移所引起的IBD严重程度低于野生型T细胞。由于Th1主调节器T-bet的表观遗传变化，CD4 + T细胞中的层状A / C缺乏增强了Treg主调节器FOXP3的转录，从而促进Treg分化，并减少了Th1极化。在肠系膜淋巴结中，CD103 +树突状细胞释放的视黄酸（RA）下调CD4 + T细胞中的层粘蛋白A / C，从而增强Treg分化。但是，非RA产生的CD103树突状细胞在外周淋巴结中占主导地位，促进lamin A / C在CD4 + T细胞中的表达，并因此促进Th1分化。我们的发现建立了lamin A / C作为生理条件下Th分化的关键调节器，并表明它是IBD中潜在的免疫调节靶标。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版