The immune system plays a key role in causing, enabling, or regulating most types of human disease. We will systematically study how immune cells change with aging and disease in a large, prospectively followed population. Our overarching objective is to develop an immune fitness atlas and identify immune alterations that can be predictive of disease over time. We will focus on autoimmune disease, cardiovascular disease, and cancer; especially hematological malignancies that are usually associated with immune alterations.
In the past decade, single!cell RNA sequencing (scRNA-seq) has triggered a true revolution in immunological research. As single!cell molecular profiling tools, scRNA!seq technologies provide a better understanding of the heterogeneity associated with individual immune cells and the responses at the molecular levels under physiological and pathological conditions. The single!cell sequencing!based studies have successfully identified new immune cell subsets and developmental trajectories. Infectious diseases, inflammation, autoimmunity, and cancers pose urgent threats to human health. How to translate our understanding of molecular mechanisms of immune regulation into clinical therapies remains a big challenge.
In this study, by performing integrative analysis between our recent large-scale scRNA-seq and T cell receptor (TCR)/B cell receptor (BCR) sequencing results on 394 peripheral blood immune cell samples and the UK Biobank study’s rich phenotypic data, including the individual’s age and disease diagnoses, we will be able to characterize immune system fitness and immune aging in this large population and identify associations that may be useful as predictive biomarkers or to inform our understanding of disease and the development of therapeutic interventions. The pilot Immune Fitness (iFit) Project will translate the lessons learned from single immune cell profiling into clinically impactful biomarkers and opportunities for drug development.
