By regulating protein degradation, constitutive proteasomes (CPs) control practically all cellular functions. In addition to CPs, vertebrates express immunoproteasomes (IPs). The major nonredundant role ascribed to IPs is their enhanced ability to generate antigenic peptides. We report that CPs and IPs differentially regulate the expression of >8000 transcripts in maturing mouse dendritic cells (DCs) via regulation of signaling pathways such as IFN regulatory factors, STATs, and NF-κB. IPs regulate the transcription of many mRNAs and maturation of a few of them. Moreover, even when engineered to present optimal amounts of antigenic peptide, IP-deficient DCs are inefficient for in vivo T cell priming. Our study shows that the role of IPs in DCs is not limited to Ag processing and reveals a major nonredundant role for IPs in transcription regulation. The dramatic effect of IPs on the transcriptional landscape could explain the various immune and nonimmune phenotypes observed in vertebrates with IP deficiency or mutations.

Excisional procedures, such as loop electrosurgery (LEEP) and cold knife conization, are recommended treatments for cervical intraepithelial dysplasia (CIN). CIN and excisional treatments are associated with an increased risk of preterm delivery and premature rupture of membranes. This association is fairly consistent across studies focusing on cold knife conization, procedures removing deeper tissue specimens, and repeat procedures. Because the association is not as strong or consistent for single, shallow LEEPs, it is possible that the increased risk may be related, at least partly, to other factors (confounding). To prevent complications, treatment guidelines should be strictly followed to minimize overtreatment. General measures to prevent preterm birth, such as screening and treating infections and smoking cessation should be considered. Given the lack of evidence on the impact of progesterone to prevent preterm delivery in this population, further studies will be needed to determine if transvaginal sonographic cervical length measurement should be offered routinely during pregnancy.

Background: By regulating protein degradation, constitutive proteasomes (CPs) regulate practically all fundamental cellular processes. Vertebrates also express immunoproteasomes (IPs), but the only well-established non-redundant role for IPs is their enhanced ability to generate peptides for MHC-I presentation. Results: Here we show that IPs regulate the expression of 8,104 genes in maturing bone marrow-derived dendritic cells (DCs). IPs regulated transcription of many mRNAs and maturation of a subset of them. These genes were separated into 15 different kinetic patterns, and Gene-Ontology analysis revealed enrichment linked to immune functions and housekeeping cellular processes, highlighting the complexity of the transcriptional cascade regulated by IPs. Notably, IPs’ impact on transcription was mediated through the non-redundant regulation of critical immune-related pathways, such as Nf-kB, STATs and IRFs. Furthermore, even when loaded with optimal amounts of SIINFEKL, IP-deficient DCs were inefficient for in vivo priming of OT-1 T cells. Conclusion: Our study shows that the role of IPs is not limited to antigen processing and highlights a new and critical role for IPs in regulation of gene expression. The dramatic impact of IPs on the transcriptional landscape could explain the various immune and non-immune phenotypes observed in vertebrates with IP-deficiency or -mutation.