CD74 regulates cellularity and maturation of medullary thymic epithelial cells partially by activating the canonical NF-κB signaling pathway
CD74 regulates cellularity and maturation of medullary thymic epithelial cells partially by activating the canonical NF-κB signaling pathway
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CD74 部分通过激活经典 NF-κB 信号通路来调节髓质胸腺上皮细胞的细胞结构和成熟
DOI：
10.1096/fj.202100139r
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Qiu Yu-Rong
中科院分区：
文献类型：
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作者：
Wang Hong-xia;Zhang Qian;Zhang Jiayu;Luan Rong;Liang Zhanfeng;Tan Liang;Xu Yanan;Zhang Peng;Zheng Lei;Zhao Yong;Qiu Yu-Rong
胸腺上皮细胞（TEC）对于T细胞发育、T细胞受体（TCR）库选择和特异性谱系分化是不可或缺的。胸腺髓质上皮细胞（mTEC）占成人TEC的大多数，对胸腺细胞选择和自身耐受至关重要。CD 74是主要组织相容性复合体II类（MHCII）的非多态性跨膜糖蛋白，在TEC中表达。然而，CD 74在调节mTEC发展中的确切作用尚不清楚。在这项研究中，我们发现CD 74的丢失导致髓质显著减少，表达CD 80分子的成熟mTEC的细胞数量选择性减少，最终导致胸腺CD 4 +T细胞发育受损。此外，RNA序列分析显示，CD 74缺陷明显下调mTECs中活化B细胞（NF-κB）的经典核因子κ轻链增强子（NF-κB）信号通路。我们的研究结果表明，CD 74积极控制mTEC细胞和成熟，部分通过激活经典的NF-κB信号通路。
Thymic epithelial cells (TECs) are indispensable for T cell development, T cell receptor (TCR) repertoire selection, and specific lineage differentiation. Medullary thymic epithelial cells (mTECs), which account for the majority of TECs in adults, are critical for thymocyte selection and self‐tolerance. CD74 is a nonpolymorphic transmembrane glycoprotein of major histocompatibility complex class II (MHCII) that is expressed in TECs. However, the exact role of CD74 in regulating the development of mTEC is poorly defined. In this research, we found that loss of CD74 resulted in a significant diminution in the medulla, a selective reduction in the cell number of mature mTECs expressing CD80 molecules, which eventually led to impaired thymic CD4+T cell development. Moreover, RNA‐sequence analysis showed that CD74 deficiency obviously downregulated the canonical nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling pathway in mTECs. Our results suggest that CD74 positively controls mTEC cellularity and maturation partially by activating the canonical NF‐κB signaling pathway.