New-onset dermatomyositis following SARS-CoV-2 infection and vaccination: a case-based review.

Dermatomyositis is a rare, type I interferon-driven autoimmune disease, which can affect muscle, skin and internal organs (especially the pulmonary system). In 2021, we have noted an increase in new-onset dermatomyositis compared to the years before the SARS-CoV-2 pandemic in our center. We present four cases of new-onset NXP2 and/or MDA5 positive dermatomyositis shortly after SARS-CoV-2 infection or vaccination.

Proteasome inhibition activates the mitochondrial pathway of apoptosis in human CD4+ T cells.

We have previously shown that inhibition of the proteolytic activity of the proteasome induces apoptosis and suppresses essential functions of activated human CD4(+) T cells, and we report now the detailed mechanisms of apoptosis following proteasome inhibition in these cells. Here we show that proteasome inhibition by bortezomib activates the mitochondrial pathway of apoptosis in activated CD4(+) T cells by disrupting the equilibrium of pro-apoptotic and anti-apoptotic proteins at the outer mitochondrial membrane (OMM) and by inducing the generation of reactive oxygen species (ROS). Proteasome inhibition leads to accumulation of pro-apoptotic proteins PUMA, Noxa, Bim and p53 at the OMM.

Proteasome inhibition suppresses essential immune functions of human CD4+ T cells.

The proteasome constitutes the central proteolytic component of the highly conserved ubiquitin-proteasome system, which is required for the maintenance and regulation of basic cellular processes, including differentiation, proliferation, cell cycling, gene transcription and apoptosis. Here we show that inhibition of proteasomal proteolytic activity by the proteasome inhibitors bortezomib and lactacystin suppresses essential immune functions of human CD4(+) T cells activated by allogeneic dendritic cells (DCs). In activated CD4(+) T cells, proteasome inhibition induces apoptosis accompanied by rapid accumulation and stabilization of the tumour suppressor protein p53.