NK cell senescence in adversity-divergent twins

Socioeconomic conditions have a significant impact on health and disease. In many cases, living in poor socioeconomic conditions is a major contributor to the cost of both acute as well as chronic care. Data from the previous FNR funded projects “EpiPath” and “MetCOEPs suggest that accelerated immunological ageing, the natural decline in immune functioning with age, may be key to understanding these health disparities. The psychosocial, socioeconomic and wider external environment influence immunosenescence and inflammaging, and have been associated with asthma, allergy, type 2 diabetes, mental disorders (depression, schizophrenia) as well as cardiovascular disease and hypertension. Poor life conditions are perhaps the most powerful driver of immuneageing. Previously we have shown how early-life adversity accelerates immunological ageing in adulthood with concurrent immunosenescence and altered numbers of circulating lymphocytes at baseline. The question remains as to whether this is limited to adversity in early-life, or whether it operates lifelong. One hundred adversity-discordant MZ twin pairs will undergo a detailed biological characterisation including a complete CyToF 30 member panel unbiased immune profiling and DNA methylation analyses in the recently funded project “ImmunoTwin”. While the ImmunoTwin project will focus on the overall immunophenotype, this PhD project will participate in ImmunoTwin data collection (CyToF), and then extract NK cell data, further exploring our recent data where psychosocial adversity reduced NK cell cytotoxicity, degranulation ability, and increased their senescence. Using Immunotwin material, scRNA-Seq will be performed on NK cells from a limited number of participants, and furthermore, epigenetic DNA methylation profiles will be obtained from selected populations.

Fernandes, S.B., et al., Unbiased Screening Identifies Functional Differences in NK Cells After Early Life Psychosocial Stress. Front Immunol, 2021. 12: p. 674532.

Elwenspoek, M.M.C., et al., Glucocorticoid receptor signaling in leukocytes after early life adversity. Dev Psychopathol, 2020. 32(3): p. 853-863.

Turner, J.D., et al., Twin Research in the Post-Genomic Era: Dissecting the Pathophysiological Effects of Adversity and the Social Environment. Int J Mol Sci, 2020. 21(9).