PSMB11 regulates gene expression in cortical thymic epithelial cells.

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.