Effect of LMP7 and MECL1-immunoproteasome subunits deficiency on the transcriptome of mouse bone marrow-derived dendritic cells

As regulators of protein degradation, proteasomes regulate practically all cellular functions. It is therefore logical to assume that replacement of the constitutive proteasome (CP) by its IFN- inducible homolog immunoproteasome (IP) could have far reaching effects on cell function. Accordingly, recent studies have revealed important roles for IPs in immune cells beyond MHC I-peptide processing. Moreover, the expression of IPs in non-immune cells from non-inflamed tissues suggests that the involvement of IPs is not limited to the immune system. We demonstrate here that IP-deficiency affects the transcription of 8104 genes in maturing dendritic cells (DCs). This occurs mainly through non-redundant regulation of key immune-related transcription factors by CPs and IPs. Additionally, IP-deficiency decreases DC''s efficiency to activate CD8+ T cells in vivo. Our study reveals that the broad cellular roles of IPs could rely on transcription regulation and, more importantly, illustrates how IP-deficiency could generate MHC I-peptide processing-independent phenotypes. Overall design: Examination of the transcriptome of WT and immunoproteasome-deficient cells at 4 different time points of dendritic cell maturation, in 4 experimental replicates (total of 32 samples).

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de Verteuil DA, Rouette A, Hardy MP, Lavallée S, Trofimov A, Gaucher É, Perreault C