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http://bura.brunel.ac.uk/handle/2438/8134
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DC Field | Value | Language |
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dc.contributor.advisor | Li, S-L | - |
dc.contributor.author | Ghaffari, Emma Louise Marie | - |
dc.date.accessioned | 2014-03-10T16:15:14Z | - |
dc.date.available | 2014-03-10T16:15:14Z | - |
dc.date.issued | 2013 | - |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/8134 | - |
dc.description | This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University. | en_US |
dc.description.abstract | Early Growth Response Genes (EGR) is a family of four transcription factors containing a unique zinc finger domain. EGR-2 and EGR-3 are important for hindbrain development and myelination. These transcription factors are also necessary for lymphocyte function however, the mechanisms are still unclear. Previous findings have shown that EGR-2cKO mice develop lupus-like autoimmune disease with high levels of pro-inflammatory cytokines despite showing normal T and B cell proliferation after mitogenic stimulation. Therefore we established the CD2-EGR-2-/-EGR-3-/- mouse model to explore the phenotype, susceptibility to autoimmune disease and relevant lymphocyte function. We discovered that CD2-EGR-2-/-EGR-3-/- mice developed severe systemic autoimmune disease and expressed high levels of inflammatory cytokines. More importantly we discovered a novel finding that CD2-EGR-2-/-EGR-3-/- T and B cells had impaired cell proliferation after mitogenic stimulation. Further investigations revealed that the molecular mechanism defected in the T cell receptor signalling pathway is due to a dysfunction in Activator Protein-1 (AP-1). AP-1 is a heterodimeric protein composed of AP-1 family members including Jun, Atf and Fos. Our data shows that EGR-2 and EGR-3 directly bind with the Atf family member Batf, which prevents Batf’s inhibitory function on AP-1 activation. This research demonstrates that EGR-2 and EGR-3 intrinsically regulate chronic inflammation and also positively regulate antigen receptor activation. In conclusion EGR-2 and EGR-3 are essential for providing optimal immune responses, whilst limiting inflammatory immunopathology. We propose that this new model could be used for studying autoimmune disease. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Brunel University School of Health Sciences and Social Care PhD Theses | - |
dc.relation.ispartof | School of Health Sciences and Social Care | - |
dc.relation.uri | http://bura.brunel.ac.uk/bitstream/2438/8134/1/FulltextThesis.pdf | - |
dc.subject | Immunology | en_US |
dc.subject | Biology | en_US |
dc.subject | Adaptive immunity | en_US |
dc.subject | T cell receptor signalling | en_US |
dc.subject | Autoimmunity | en_US |
dc.title | Early growth response genes -2 and -3 are essential for optimal immune responses | en_US |
dc.type | Thesis | en_US |
Appears in Collections: | Biological Sciences Dept of Life Sciences Theses |
Files in This Item:
File | Description | Size | Format | |
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FulltextThesis.pdf | 1.6 MB | Adobe PDF | View/Open |
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