The proprotein convertase furin regulates the development of thymic epithelial cells to ensure central immune tolerance

The generation of mature T cells and establishment of central tolerance is predominantly orchestrated by thymic epithelial cells (TECs). Proprotein convertases are responsible for the proteolysis of proproteins into their mature bioactive counterparts. Here, we found that Furin, a member of the subtilisin/kexin-like PCs family, is highly expressed in TECs compared with other members of this family. TEC-specific deletion of Furin caused severe thymic atrophy and predominantly reduced the number of medullary TECs and thymic tuft cells, and to a less degree, cortical TECs. Furin deletion attenuated the proliferation of TECs, impaired thymopoiesis, and led to autoimmune disorders in mice. Furin promotes the development of TECs via cleavage of proIGF1 receptor and pro-Insulin receptor and the activation of downstream ERK/MAPK and Akt signaling pathways. Thus, this study uncovered the role of furin in TEC development and function and highlighted the importance of post-translational modification of immature proproteins in TEC biology.

Automated summary

The study revealed that Furin is highly expressed in thymic epithelial cells (TECs) and its deletion leads to reduced TECs, thymic atrophy, impaired thymopoiesis, and autoimmune disorders. Furin promotes TEC development through the cleavage of proproteins and activation of signaling pathways. This study highlights the importance of post-translational modification of immature proproteins in TEC biology.