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Publication : Ubiquitin Specific Protease 1 Expression and Function in T Cell Immunity.

First Author  Omilusik KD Year  2021
Journal  J Immunol Volume  207
Issue  5 Pages  1377-1387
PubMed ID  34380645 Mgi Jnum  J:309127
Mgi Id  MGI:6756255 Doi  10.4049/jimmunol.2100303
Citation  Omilusik KD, et al. (2021) Ubiquitin Specific Protease 1 Expression and Function in T Cell Immunity. J Immunol 207(5):1377-1387
abstractText  T cells are essential mediators of immune responses against infectious diseases and provide long-lived protection from reinfection. The differentiation of naive to effector T cells and the subsequent differentiation and persistence of memory T cell populations in response to infection is a highly regulated process. E protein transcription factors and their inhibitors, Id proteins, are important regulators of both CD4(+) and CD8(+) T cell responses; however, their regulation at the protein level has not been explored. Recently, the deubiquitinase USP1 was shown to stabilize Id2 and modulate cellular differentiation in osteosarcomas. In this study, we investigated a role for Usp1 in posttranslational control of Id2 and Id3 in murine T cells. We show that Usp1 was upregulated in T cells following activation in vitro or following infection in vivo, and the extent of Usp1 expression correlated with the degree of T cell expansion. Usp1 directly interacted with Id2 and Id3 following T cell activation. However, Usp1 deficiency did not impact Id protein abundance in effector T cells or alter effector T cell expansion or differentiation following a primary infection. Usp1 deficiency resulted in a gradual loss of memory CD8(+) T cells over time and reduced Id2 protein levels and proliferation of effector CD8(+) T cell following reinfection. Together, these results identify Usp1 as a player in modulating recall responses at the protein level and highlight differences in regulation of T cell responses between primary and subsequent infection encounters. Finally, our observations reveal differential regulation of Id2/3 proteins between immune versus nonimmune cell types.
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