Year: 2012
Type: dissertation
Abstract: p15Ink4b, an inhibitor of cyclin-dependent kinases, is a tumor suppressor frequently associated with hematological malignancies.Its inactivation through DNA methylation is one of the most prevalent epigenetic alterations reported in up to 80% of all acute myeloid leukemia (AML) patients.During the leukemogenesis process, escape of pre-leukemic cells from immune clearance represents an important step in the establishment of leukemic disease.Dendritic cells (DCs) are potent antigen-presenting cells (APC) that play critical roles in the regulation of immune responses.Their primary function is to stimulate naïve T cells against pathogens and cancerous cells leading to their effective clearance.We wished to investigate the role that p15Ink4b might be playing during the development and maturation of conventional DCs (cDCs).We found that expression of p15Ink4b is strongly induced in a biphasic manner during the development and activation of bone marrow-derived DCs (BM-DCs), suggesting an important role for p15Ink4b in DC maturation.Also, myeloid-specific deletion of p15Ink4b in mice resulted in significantly fewer and less mature conventional DCs (cDCs) as compared to wild type mice.Consistent with this data, BM cells from knockout mice cultured in-vitro generated fewer numbers of BM-DCs that express lower levels of the antigen presenting (MHC vii laughter during the worst moments of this thesis, and I could always count on them to jump in with excitement when I hit major milestones.I greatly value their friendship and deeply appreciate their belief in me.
Author: Joanna Fares
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2283475309