Wang Hong-Xia, Zhang Qian, Zhang Jiayu, Luan Rong, Liang Zhanfeng, Tan Liang, Xu Yanan, Zhang Peng, Zheng Lei, Zhao Yong, Qiu Yu-Rong
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Transplantation Biology Research Division, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
FASEB J. 2021 May;35(5):e21535. doi: 10.1096/fj.202100139R.
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.
胸腺上皮细胞（TECs）对于T细胞发育、T细胞受体（TCR）库选择以及特定谱系分化而言不可或缺。髓质胸腺上皮细胞（mTECs）在成体TECs中占大多数，对胸腺细胞选择和自身耐受性至关重要。CD74是主要组织相容性复合体II类（MHCII）的一种非多态性跨膜糖蛋白，在TECs中表达。然而，CD74在调节mTEC发育中的确切作用尚不清楚。在本研究中，我们发现CD74缺失导致髓质显著减少，表达CD80分子的成熟mTECs细胞数量选择性减少，最终导致胸腺CD4 T细胞发育受损。此外，RNA序列分析表明，CD74缺陷明显下调了mTECs中活化B细胞的经典核因子κB轻链增强子（NF-κB）信号通路。我们的结果表明，CD74通过激活经典NF-κB信号通路部分正向调控mTEC细胞数量和成熟。
