Metabolic Functions of the Murine Lupus Susceptibility Gene Pbx1
DC Field | Value | Language |
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dc.contributor.author | Roach, Tracoyia A. | - |
dc.contributor.author | Titov, Anton | - |
dc.contributor.author | Soh, Sujung | - |
dc.contributor.author | Robusto, Brian | - |
dc.contributor.author | Morel, Laurence | - |
dc.date.available | 2021-02-22T09:45:32Z | - |
dc.date.issued | 2018-05 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.issn | 1550-6606 | - |
dc.identifier.uri | https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/4542 | - |
dc.description.abstract | Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects many organ systems. Poorly characterized genetic factors contribute to SLE, in part through the production of autoreactive or inflammatory T cells. Pre-B cell leukemia homeobox 1 (Pbx1) is a transcription factor whose Pbx1-d dominant negative splice isoform is overexpressed in CD4T cells of lupus patients as well as in the NZM2410 lupus-prone mouse as compared to the normal Pbx1-b isoform. Based on gene expression studies comparing murine CD4 T cells overexpressing Pbx1-d to controls, we hypothesize that Pbx1-d enhances cellular metabolism in T cells through the HIF1α and mTORc1 pathways. CD4 T cells expressing Pbx1-d present a higher cellular metabolism and show a higher mTORc1 activation than normal control T cells. Using mesenchymal stem cells, we showed that transfection of Pbx1-d was sufficient to increase glycolysis, a pathway linked to T cell activation. We found that Ddit4, an mTORc1 inhibitor, shows a lower expression in the Pbx1-d-expressing CD4 T cells than in normal T cells. We also discovered that Pbx1-d preferentially binds to the promoter of Ddit4, as well as Egln1 and Egln3, two HIF1a inhibitors. These results suggest that a mechanism by which the Pbx1-d allele contributes to lupus pathogenesis is to enhance CD4 T cell metabolism. Future work will define how Pbx1 controls the immune system and how the function of this transcription factor is linked to cellular metabolism. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | AMER ASSOC IMMUNOLOGISTS | - |
dc.title | Metabolic Functions of the Murine Lupus Susceptibility Gene Pbx1 | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.wosid | 000459977701015 | - |
dc.identifier.bibliographicCitation | JOURNAL OF IMMUNOLOGY, v.200, no.1 suppl. | - |
dc.citation.title | JOURNAL OF IMMUNOLOGY | - |
dc.citation.volume | 200 | - |
dc.citation.number | 1 suppl. | - |
dc.type.docType | Meeting Abstract | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.identifier.url | https://www.jimmunol.org/content/200/1_Supplement/100.19 | - |
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