The role of Toll-like receptors in senescence of immune cells
Školitel: Mgr. Jan Frič, Ph.D.
Instituce: Masaryk University, Faculty of Medicine
Obor: Medical Biology
O mém projektu
The significant aging of population across the globe strengthened the need to understand the molecular mechanism of aging processes and linked pathologies. Senescence of immune cells is phenomenon associated with aging of organism. Immunosenescence is characterised by decline of plethora of immune functions including adaptive as well as innate responses. Immunosenescence is also associated to number of pathologies including higher susceptibility to infections and cardiovascular diseases linked to cancer therapy and age-associated diseases. While senescence of adaptive immunity is relatively well described, mechanism of aging-related senescence in myeloid cells is only poorly understood. Chronic inflammation has negative impact to many aspects of immune responses including immune cells development and function, chronic inflammation has been associated to immunosenescence. Aim of this project is to use in vitro model of myelopoiesis of human induced-pluripotent stem cells, challenge the differentiation process with long-term stimulation of Toll-like receptors (TLRs) to mimic chronic inflammation and dissect the molecular mechanism of the onset of senescence. Damage-associated molecular patterns (DAMPs) able to engage with TLRs will be studied along in plasma samples of neuroblastoma patients to associate the impact of DAMPs generated in therapy to cell senescence. This project could point out the key factors responsible for immune cell senescence in chronic low-grade inflammation and elucidate the role of TLRs in cancer therapy-related premature aging.