Expression of CSI and 2B4 in Human Lupus Erythematosus and Transcriptional Regulation of CSI Gene
| dc.contributor.advisor | Porunelloor Mathew | |
| dc.creator | Kim, Jongrok | |
| dc.date.accessioned | 2019-08-22T21:25:35Z | |
| dc.date.available | 2019-08-22T21:25:35Z | |
| dc.date.issued | 2010-07-01 | |
| dc.date.submitted | 2013-05-10T13:48:04-07:00 | |
| dc.description.abstract | Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by production of pathogenic autoantibodies that affect multiple organs. Signaling lymphocyte activation molecule (SLAM) family receptors play critical roles in the regulation of hematopoietic cells, and polymorphisms in these receptors were found to be associated with susceptibility to SLE. In addition, the differential expression of splice variants of one member of SLAM family receptors was shown to be responsible for lupus development in mice. Since the important roles of SLAM family receptors 2B4 and CS1 in immune regulation are expanding, we compared the expression of 2B4 and CS1 in peripheral blood mononuclear cells (PBMCs) from SLE patients with those of healthy individuals. While alterations of the expression of 2B4 and CS1 were observed in SLE, most strikingly, a linear relationship was found between the proportion of CS1-expressing B cells and SLE disease activity index (SLEDAI). In particular, CS1-high expressing B cells were phenotypically similar with recently described plasmablasts, which were also shown to correlate with disease severity. Since CS1 is self-ligand and homotypic interaction of CS1-expressing B cells can trigger expansion of B cells, these results emphasize the role of CS1 in B cell-mediated diseases. Therefore, the transcriptional regulation of CS1 gene was investigated. DNA elements at -405 to +92 region of the CS1 promoter positively regulated CS1 expression. Interestingly, electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that the plasma cell specific-transcription factor Blimp-1 binds to the CS1 promoter region. Further analysis of expression and transcriptional regulation of CS1 in B cells will provide valuable information for the treatment of B-cell mediated diseases such as SLE and multiple myeloma. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12503/29323 | |
| dc.language.iso | en | |
| dc.provenance.legacyDownloads | 221 | |
| dc.subject | Genetics | |
| dc.subject | Medicine and Health Sciences | |
| dc.subject | Genetics | |
| dc.subject | sle | |
| dc.subject | lupus | |
| dc.subject | lupus erythematosus | |
| dc.title | Expression of CSI and 2B4 in Human Lupus Erythematosus and Transcriptional Regulation of CSI Gene | |
| dc.type | Dissertation | |
| dc.type.material | text | |
| thesis.degree.department | Graduate School of Biomedical Sciences | |
| thesis.degree.grantor | University of North Texas Health Science Center at Fort Worth | |
| thesis.degree.name | Doctor of Philosophy |
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