Institute for Research in Immunology and Cancer, Montreal, QC H3C 3J7, Canada; Department of Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada.
Institute for Research in Immunology and Cancer, Montreal, QC H3C 3J7, Canada.
Cell Rep. 2021 Sep 7;36(10):109546. doi: 10.1016/j.celrep.2021.109546.
The PSMB11 proteasomal subunit, expressed only in cortical thymic epithelial cells (cTECs), is essential for the development of functional CD8 T cells. An attractive yet unproven theory holds that PSMB11 generates unique major histocompatibility complex class I (MHC I)-associated peptides required for positive selection. We recently reported that PSMB11 regulates the expression of hundreds of genes in cTECs, mainly by differential proteolysis of transcription factors. Thereby, PSMB11 maintains the distinctness of cTECs relative to medullary TECs (mTECs) and promotes cortex-to-medulla migration of developing thymocytes. These conclusions have been challenged by Ohigashi and colleagues, who suggest that their data show that PSMB11 uniquely controls antigen presentation without affecting cTEC biology. Here, we perform a comprehensive reanalysis of transcriptomic and proteomic data from the Ohigashi lab and confirm our original conclusions. This Matters Arising paper is in response to Ohigashi et al. (2019), published in Cell Reports. See also the response by Ohigashi and Takahama (2021), published in this issue of Cell Reports.
PSMB11 蛋白酶体亚基仅在皮质胸腺上皮细胞 (cTEC) 中表达，对于功能性 CD8 T 细胞的发育是必不可少的。一个有吸引力但未经证实的理论认为，PSMB11 产生独特的主要组织相容性复合体 I (MHC I) 相关肽，这些肽是阳性选择所必需的。我们最近报道称，PSMB11 调节 cTEC 中数百个基因的表达，主要通过转录因子的差异蛋白水解来实现。因此，PSMB11 保持了 cTEC 相对于 medullary TECs (mTECs) 的独特性，并促进了发育中的胸腺细胞从皮质向髓质的迁移。这些结论受到了 Ohigashi 及其同事的挑战，他们的数据表明 PSMB11 独特地控制抗原呈递而不影响 cTEC 生物学。在这里，我们对 Ohigashi 实验室的转录组和蛋白质组数据进行了全面的重新分析，并证实了我们的原始结论。本争议解决文章是对 Ohigashi 等人发表在《Cell Reports》上的文章的回应。另见 Ohigashi 和 Takahama 在本期《Cell Reports》上发表的回应。
