The role of transcriptional factor ETS2 repressor factor (ERF) in maturation and activation of T lymphocytes (Doctoral thesis)
ERF (ETS2 Repressor Factor) is a ubiquitously expressed transcriptional repressor of the ETS family that is regulated by subcellular localization as a result of Erk-dependent phosphorylation. It is well established that Erk1/2 plays an important role in T cell maturation and differentiation, however, its effectors are not well known. In the present dissertation, we studied the role of Erf, in vivo, in T cell maturation, using Erf floxed mice to produce thymus-specific ERF knockouts, and in vitro we studied ERF phosphorylation and function in the T cell line HuT78 over-expressing ERF. We observed statistically significant decreased numbers of CD4+ and TCRβ subpopulation and statistically significant elevated numbers of DP (CD4+CD8+) cells in the thymus of Erf deficient mice. Thus, our findings suggest that Erf is involved in T cell maturation at the DP stage, acting as a positive regulator during CD4 lineage commitment. Investigating the mechanism of Erf function, we focused on the expression of critical genes during lineage commitment and found that Gata3, ThPOK and Socs1 expression was statistically significant decreased in Erf deficient mice. Since those genes induce CD4 commitment, our findings are consistent with the hypothesis that Erf is a positive regulator of helper lineage commitment. Taking into consideration that Gata3 directly induces ThPOK expression and ThPOK regulates positively Socs1 expression, we propose that Erf acts as an upstream direct or indirect activator of Gata3. In an attempt to explore the possible impact of ERF in the biology of peripheral T lymphocytes, we studied the expression of ERF in the HuT78 cell line. Our results showed that ERF phosphorylation and subcellular localization is an Erk-dependent event. We also have indications that ERF act as a repressor of cell cycle. Finally, cells over-expressing ERF showed statistically significant lower IL-2 production, suggesting that ERF acts as a negative regulator of IL-2, something particularly interesting since IL-2 is a cytokine with broad range of immunological functions. Overall, our results show, for the first time, the possible involvement of ERF in T cell biology and can be the trigger for further research to understand thymocyte maturation and to comprehend the role of ERF in other immunological processes such as the differentiation of T helper cells (TH).
|Institution and School/Department of submitter:||Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιών|
|Keywords:||Μεταγραφικός παράγοντας ERF,Τ λεμφοκύτταρα,Ωρίμανση,Ενεργοποίηση|
|Appears in Collections:||Διδακτορικές Διατριβές|
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|Δ.Δ. ΤΣΙΟΜΗΤΑ ΣΤΑΥΡΟΥΛΑ 2018.pdf||4.72 MB||Adobe PDF||View/Open|
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