Foxa1 and Foxa2 in thymic epithelial cells (TEC) regulate medullary TEC and regulatory T-cell maturation.
Foxa1 and Foxa2 in thymic epithelial cells (TEC) regulate medullary TEC and regulatory T-cell maturation.
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DOI：
10.1016/j.jaut.2018.07.009
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发表时间：
2018-09
影响因子：
12.8
通讯作者：
Crompton T
中科院分区：
文献类型：
--
作者：
Lau CI;Yánez DC;Solanki A;Papaioannou E;Saldaña JI;Crompton T
Foxa1和Foxa2转录因子对小鼠发育至关重要。在这里，我们表明，他们表达在胸腺上皮细胞（TEC），他们调节TEC的发展和功能，与T细胞的发展的重要后果。TEC对于T细胞分化、谱系决定和库选择是必需的。从小鼠TEC中有条件地删除Foxa1和Foxa2导致较小的胸腺，具有更大比例的TEC和更大比例的髓质与皮质TEC。细胞表面MHCI表达增加皮质TEC在条件Foxa1Foxa2敲除胸腺，MHCII表达减少皮质和髓质TEC人口。TEC分化和MHC表达的这些变化导致胸腺细胞数量显著减少，CD4+CD8+细胞对CD4谱系的阳性选择减少，并且CD8细胞分化增加。从TEC中有条件地缺失Foxa1和Foxa2也导致髓质TEC群体的增加，并且Aire的表达增加，但是表达Aire的mTEC上的细胞表面MHCII表达降低，并且调节性T细胞的产生增加。因此，TEC中的Foxa1和Foxa2促进CD4SP T细胞的阳性选择，并调节调节性T细胞的产生和活性，这对自身免疫很重要。Foxa1和Foxa2控制胸腺上皮细胞分化和T细胞选择。胸腺上皮细胞中的Foxa1和Foxa2调节调节性T细胞的产生。从TEC中删除Foxa1和Foxa2增强Treg活性。
The Foxa1 and Foxa2 transcription factors are essential for mouse development. Here we show that they are expressed in thymic epithelial cells (TEC) where they regulate TEC development and function, with important consequences for T-cell development. TEC are essential for T-cell differentiation, lineage decisions and repertoire selection. Conditional deletion of Foxa1 and Foxa2 from murine TEC led to a smaller thymus with a greater proportion of TEC and a greater ratio of medullary to cortical TEC. Cell-surface MHCI expression was increased on cortical TEC in the conditional Foxa1Foxa2 knockout thymus, and MHCII expression was reduced on both cortical and medullary TEC populations. These changes in TEC differentiation and MHC expression led to a significant reduction in thymocyte numbers, reduced positive selection of CD4+CD8+ cells to the CD4 lineage, and increased CD8 cell differentiation. Conditional deletion of Foxa1 and Foxa2 from TEC also caused an increase in the medullary TEC population, and increased expression of Aire, but lower cell surface MHCII expression on Aire-expressing mTEC, and increased production of regulatory T-cells. Thus, Foxa1 and Foxa2 in TEC promote positive selection of CD4SP T-cells and modulate regulatory T-cell production and activity, of importance to autoimmunity. Foxa1 and Foxa2 control thymic epithelial cell differentiation and T-cell selection. Foxa1 and Foxa2 in thymic epithelial cells modulate regulatory T-cell production. Deletion of Foxa1 and Foxa2 from TEC enhances Treg activity.
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影响因子：
4
作者：
Furmanski AL;Barbarulo A;Solanki A;Lau CI;Sahni H;Saldana JI;D'Acquisto F;Crompton T
通讯作者：
Crompton T
影响因子：
--
作者：
Lau CI;Barbarulo A;Solanki A;Saldaña JI;Crompton T
通讯作者：
Crompton T
影响因子：
4.4
作者：
Hager-Theodorides, Ariadne L.;Furmanski, Anna L.;Crompton, Tessa
通讯作者：
Crompton, Tessa
影响因子：
20.3
作者：
Lau, Ching-in;Outram, Susan V.;Crompton, Tessa
通讯作者：
Crompton, Tessa
影响因子：
20.3
作者：
Hager-Theodorides, AL;Dessens, JT;Crompton, T
通讯作者：
Crompton, T