Intersection of population variation and autoimmunity genetics in human T cell activation
T lymphocyte activation by antigen conditions adaptive immune responses and immunopathologies, but we know little about its variation in humans and its genetic or environmental roots. We analyzed gene expression in CD4(+) T cells during unbiased activation or in T helper 17 (T(H)17) conditions from 348 healthy participants representing European, Asian, and African ancestries. We observed interindividual variability, most marked for cytokine transcripts, with clear biases on the basis of ancestry, and following patterns more complex than simple T(H)1/2/17 partitions. We identified 39 genetic loci specifically associated in cis with activated gene expression. We further fine-mapped and validated a single-base variant that modulates YY1 binding and the activity of an enhancer element controlling the autoimmune-associated IL2RA gene, affecting its activity in activated but not regulatory T cells. Thus, interindividual variability affects the fundamental immunologic process of T helper activation, with important connections to autoimmune disease.
Research Papers
- Conjunction of factors triggering waves of seasonal influenza
- Algorithmic Bio-surveillance For Precise Spatio-temporal Prediction of Zoonotic Emergence
- Profiling Reactive Metabolites via Chemical Trapping and Targeted Mass Spectrometry
- Does the brain listen to the gut?
- (Meta)genomic insights into the pathogenome of Cellulosimicrobium cellulans
- A robust adaptive denoising framework for real-time artifact removal in scalp EEG measurements
- Imputing Gene Expression in Uncollected Tissues Within and Beyond GTEx
- Small Rad51 and Dmc1 Complexes Often Co-occupy Both Ends of a Meiotic DNA Double Strand Break
- Controlling the Cyanobacterial Clock by Synthetically Rewiring Metabolism
- Choosing experiments to accelerate collective discovery
