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| Identifier |
000382576 |
| Title |
Study of the role of AKT kinase in the differentiation and function of myeloid derived suppressor cells (MDSCs) |
| Alternative Title |
Μελέτη του ρόλου της κινάσης Akt στην διαφοροποίηση και στη δράση των κατασταλτικών κυττάρων μυελικής σειράς (MDSCs) |
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Author
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Πίκουλας, Αντώνιος Ι
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Thesis advisor
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Βεργίνης, Πάνος
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Reviewer
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Τσατσάνης, Χρήστος
Ηλιόπουλος, Άρης
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| Abstract |
Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of immature cells generating from the bone marrow that have the ability under certain conditions to suppress the immune response. MDSCs contribute to the negative regulation of the immune response by suppressing the T-cell mediated responses and also by interacting with various other cells of the immune system. Although at the beginning these cells were only studied in various cancer models where their importance was proven, in the past few years, evidence is gathering from in vitro and in vivo studies concerning and underlining the important role of MDSCs’ function or loss of function in various pathological conditions.
Akt kinase is one of the most important and known protein kinases of the eukaryotic cells. It is a central node for many signaling pathways in the cell and is activated after a variety of stimulatory molecules that reach the surface of cells. Three different isoforms are known and all of them have specific and also overlapping roles in many pathways. The importance of these kinases roles can be understood examining the phenotype and the pathology of Akt KO animals that depends on which Akt kinase isoform is absent.
This study aims to elucidate the role that two of the Akt isoforms have at the differentiation and function of MDSCs either in the bone marrow where these cells come from or in the periphery where they migrate in order to suppress an immune response or home until needed to suppress a response. In order to understand the role that Akt proteins have at the differentiation and function of MDSCs, Akt KO mice were used. The percentages of MDSCs were countered at both Akt1-/- and Akt2-/- mice in both bone marrow and spleen tissues and compared with B6 mice using two different conditions: naïve mice and mice that were immune triggered. Differences at different strains were revealed at both conditions that could indicate a role for Akt proteins at the maturation and proliferation of MDSCs. Also morphological differences were found between MDSCs isolated from Akt1-/- mice and B6 mice. Furthermore, the suppressive function of Akt-/- MDSCs seem to be altered compared to B6 mice, as results from co-culturing of these cells with T-cells show and also arginase1 and CEBPb expression levels differences reveal.
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In conclusion, these data demonstrate differences at the numbers of MDSCs in the absence of Akt proteins and also morphological alterations and differences at the suppressive ability of these cells.
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| Language |
English |
| Subject |
AKt |
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Differentiation |
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Function |
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MDSCs |
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Διαφοροποίηση |
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Κατασταλτικά κύτταρα μυελικής σειράς |
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Κινάση |
| Issue date |
2014-01-22 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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| Views |
208 |
Study of the role of AKT kinase in the differentiation and function of myeloid derived suppressor cells (MDSCs)
