Ask about this productRelated genes to: PSMB11 antibody
- Gene:
- PSMB11 NIH gene
- Name:
- proteasome subunit beta 11
- Previous symbol:
- -
- Synonyms:
- beta5t
- Chromosome:
- 14q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 2008-01-21
- Date modifiied:
- 2016-04-04
Related products to: PSMB11 antibody
Related articles to: PSMB11 antibody
- Pregnancy causes abrupt thymic atrophy. This atrophy is characterized by a severe decrease in the number of all thymocyte subsets and qualitative (but not quantitative) changes in thymic epithelial cells (TECs). Pregnancy-related thymic involution is triggered by progesterone-induced functional changes affecting mainly cortical TECs (cTECs). Remarkably, this severe involution is rapidly corrected following parturition. We postulated that understanding the mechanisms of pregnancy-related thymic changes could provide novel insights into signaling pathways regulating TEC function. When we analyzed genes whose expression in TECs was modified during late pregnancy, we found a strong enrichment in genes bearing KLF4 transcription factor binding motifs. We, therefore, engineered a mouse model to study the impact of TEC-specific deletion in steady-state conditions and during late pregnancy. Under steady-state conditions, deletion had a minimal effect on TEC subsets and did not affect thymic architecture. However, pregnancy-induced thymic involution was much more pronounced in pregnant females lacking expression in TECs. These mice displayed a substantial ablation of TECs with a more pronounced loss of thymocytes. Transcriptomic and phenotypic analyses of TECs revealed that maintains cTEC numbers by supporting cell survival and preventing epithelial-to-mesenchymal plasticity during late pregnancy. We conclude that is essential for preserving TEC's integrity and mitigating thymic involution during late pregnancy. - Source: PubMed
Publication date: 2023/04/27
Depoërs LucyleDumont-Lagacé MaudeTrinh Vincent Quoc-HuyHouques ChloéCôté CarolineLarouche Jean-DavidBrochu SylviePerreault Claude - In the thymus, cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells support αβT cell development from lymphoid progenitors. For cTECs, expression of a specialized gene signature that includes , , and enables the cortex to support T lineage commitment and the generation and selection of CD4CD8 thymocytes. Although the importance of cTECs in T cell development is well defined, mechanisms that shape the cTEC compartment and regulate its functional specialization are unclear. Using a reporter mouse model, we show that changes in expression reveal a developmentally regulated program of cTEC heterogeneity. Although cTECs are uniformly during neonatal stages, progression through postnatal life triggers the appearance of cTECs that continue to reside in the cortex alongside their counterparts. This appearance of cTECs is controlled by maturation of CD4CD8, but not CD4CD8, thymocytes, demonstrating that stage-specific thymocyte cross-talk controls cTEC heterogeneity. Importantly, although fate-mapping experiments show both and cTECs share a common cell origin, RNA sequencing analysis shows cTECs no longer express , which results in loss of the FOXN1-dependent cTEC gene signature and may explain the reduced capacity of cTECs for thymocyte interactions. In summary, our study shows that shaping of the cTEC compartment during the life course occurs via stage-specific thymocyte cross-talk, which drives loss of expression and its key target genes, which may then determine the functional competence of the thymic cortex. - Source: PubMed
Publication date: 2022/11/14
White Andrea JParnell Sonia MHandel AdamMaio StefanoBacon AndreaCosway Emilie JLucas BethJames Kieran DCowan Jennifer EJenkinson William EHollander Georg AAnderson Graham - The PSMB11 proteasomal subunit, expressed only in cortical thymic epithelial cells (cTECs), is essential for the development of functional CD8 T cells. An attractive yet unproven theory holds that PSMB11 generates unique major histocompatibility complex class I (MHC I)-associated peptides required for positive selection. We recently reported that PSMB11 regulates the expression of hundreds of genes in cTECs, mainly by differential proteolysis of transcription factors. Thereby, PSMB11 maintains the distinctness of cTECs relative to medullary TECs (mTECs) and promotes cortex-to-medulla migration of developing thymocytes. These conclusions have been challenged by Ohigashi and colleagues, who suggest that their data show that PSMB11 uniquely controls antigen presentation without affecting cTEC biology. Here, we perform a comprehensive reanalysis of transcriptomic and proteomic data from the Ohigashi lab and confirm our original conclusions. This Matters Arising paper is in response to Ohigashi et al. (2019), published in Cell Reports. See also the response by Ohigashi and Takahama (2021), published in this issue of Cell Reports. - Source: PubMed
Apavaloaei AncaLaverdure Jean-PhilippePerreault Claude - β5t is a cortical thymic epithelial cell (cTEC)-specific component of the thymoproteasome, which is essential for the optimal production of functionally competent CD8 T cells. Our recent analysis showed a specific impact of β5t on proteasome subunit composition in cTECs, supporting the possibility that the thymoproteasome optimizes CD8 T cell development through the production of MHC-I-associated unique self-peptides in cTECs. However, a recent article reports that β5t regulates the expression of hundreds of cTEC genes and affects both CD4 and CD8 thymocytes by causing oxidative stress in thymocytes. The authors further analyze our published data and describe that they confirm their conclusions. Here, we examine the issues that they raise and conclude that, rather than regulating hundreds of genes in cTECs, β5t has a highly specific impact in cTECs on proteasome subunit composition. This Matters Arising Response article addresses the Apavaloaei et al. (2021) Matters Arising paper, published concurrently in Cell Reports. - Source: PubMed
Ohigashi IzumiTakahama Yousuke - The thymus prevents autoimmune diseases through mechanisms that operate in the cortex and medulla, comprising positive and negative selection and the generation of regulatory T-cells (Tregs). Egress from the thymus through the perivascular space (PVS) to the blood is another possible checkpoint, as shown by some autoimmune/immunodeficiency syndromes. In polygenic autoimmune diseases, subtle thymic dysfunctions may compound genetic, hormonal and environmental cues. Here, we cover (a) tolerance-inducing cell types, whether thymic epithelial or tuft cells, or dendritic, B- or thymic myoid cells; (b) tolerance-inducing mechanisms and their failure in relation to thymic anatomic compartments, and with special emphasis on human monogenic and polygenic autoimmune diseases and the related thymic pathologies, if known; (c) polymorphisms and mutations of tolerance-related genes with an impact on positive selection (e.g. the gene encoding the thymoproteasome-specific subunit, PSMB11), promiscuous gene expression (e.g. AIRE, PRKDC, FEZF2, CHD4), Treg development (e.g. SATB1, FOXP3), T-cell migration (e.g. TAGAP) and egress from the thymus (e.g. MTS1, CORO1A); (d) myasthenia gravis as the prototypic outcome of an inflamed or disordered neoplastic 'sick thymus'. - Source: PubMed
Publication date: 2021/02/03
Marx AlexanderYamada YosukeSimon-Keller KatjaSchalke BertholdWillcox NickStröbel PhilippWeis Cleo-Aron