Epigenetic analysis of human γδ T lymphocytes
Human γδ T-cells have emerged as key players in diverse immune responses both in health and disease. Such a dynamic functional diversity of cells is controlled at various levels of epi)genetic regulation in an orchestrated manner. However, a comprehensive overview of epigenetic mechanisms dictating human γδ T-cell development, regulation and molecular function is largely missing. The present thesis aims at elucidating the epigenetic landscape of human γδ T-cells by mainly two distinct approaches. In a first approach based on in vitro culture, the NKG2D ligand expression and release, and its further implications on NKG2D receptor expression by epigenetic inhibitors such as histone deacetylase inhibitor valproic acid, a drug widely used in the clinic, was studied. The modulation of NKG2D receptor expression and function of γδ T cells in co-culture with pancreatic carcinoma and prostate carcinoma tumor cell lines were addressed. Additionally, the effect on functional responses of γδ T-cells upon treatment with valproic acid provided new insight into γδ T-cell subset-specific responses. Specifically, valproic acid induced changes in molecular and cellular responses of human γδ T-cells, specifically by enhanced expression of the non-secretory form of IL-4, regulation of cell death and induction of global histone acetylation (H3K9ac) [...]
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