IFN-λ Enhances Constitutive Expression of MHC Class I Molecules on Thymic Epithelial Cells
IFN-λ Enhances Constitutive Expression of MHC Class I Molecules on Thymic Epithelial Cells
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DOI：
10.4049/jimmunol.2000225
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发表时间：
2020-09-01
影响因子：
4.4
通讯作者：
Perreault, Claude
中科院分区：
文献类型：
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作者：
Benhammadi, Mohamed;Mathe, Justine;Perreault, Claude
MHC-I类分子(MHC-I)的表达调控几乎只在血淋巴细胞中被研究过。我们报道，胸腺上皮细胞(TECs)，特别是髓质TECs，结构性地表达高达100倍于皮肤、结肠和肺上皮细胞(ECs)的细胞表面MHC I蛋白。原代内皮细胞表面MHC I的差异丰度是通过MHC I和MHC I结合肽相关基因的转录来调节的。Ifnarl或Ifngr1基因缺失不影响TEC中MHC I的高表达，但Aire、Ifnlr1、STAT1或Nlrc5基因缺失可使其表达减弱，并且主要由髓质TECs产生的III型干扰素驱动。Ifnlr1(-/-)小鼠表现出CD8胸腺细胞的负选择受损，并在9个月龄时出现自身免疫表现。我们的研究显示，来自不同部位的内皮细胞MHC I的表达发生了意想不到的变化，并提供了令人信服的证据，表明在TEC中MHC I的高表达对于正确的胸腺细胞教育至关重要。
Regulation of MHC class I (MHC I) expression has been studied almost exclusively in hematolymphoid cells. We report that thymic epithelial cells (TECs), particularly the medullary TECs, constitutively express up to 100-fold more cell surface MHC I proteins than epithelial cells (ECs) from the skin, colon, and lung. Differential abundance of cell surface MHC I in primary ECs is regulated via transcription of MHC I and of genes implicated in the generation of MHC I-binding peptides. Superior MHC I expression in TECs is unaffected by deletion of Ifnarl or Ifngrl, but is lessened by deletion of Aire, Ifnlr1, Stat1, or Nlrc5, and is driven mainly by type III IFN produced by medullary TECs. Ifnlr1(-/-) mice show impaired negative selection of CD8 thymocytes and, at 9 mo of age, present autoimmune manifestations. Our study shows unanticipated variation in MHC I expression by ECs from various sites and provides compelling evidence that superior expression of MHC I in TECs is crucial for proper thymocyte education.