Immunoproteasome inhibition triggers protein stress and apoptosis in cells of B cell lineage without impairing vaccination-induced antibody responses.

ABSTRACT: The immunoproteasome (IP) is a specialized form of the 26S proteasome, in which the catalytic subunits β1c, β2c, and β5c of the standard proteasome are replaced by LMP2, MECL-1, and LMP7. The IP is constitutively expressed in hematopoietic cells and its expression in non-hematopoietic cells can be induced by IFN-γ. The IP plays a crucial role in different immune functions, including MHC class-I ligand generation, cytokine production, and T helper cell differentiation. Selective inhibition of the IP has shown therapeutic benefits in treating different autoimmune diseases in pre-clinical animal models. However, the effect of IP inhibition on antibody production in viral infection and vaccination has remained underexplored. In this study, we used ONX 0914, an LMP7/LMP2-selective inhibitor of

SUBMITTER: Mink D 

PROVIDER: S-EPMC12644917 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature