Chromatin activity at GWAS loci identifies T cell states driving complex immune diseases

Blagoje Soskic, Eddie Cano-Gamez, Deborah J. Smyth, Wendy C. Rowan, Nikolina Nakic, Jorge Esparza-Gordillo, Lara Bossini-Castillo, David F. Tough, Christopher G. C. Larminie, Paola G. Bronson, David Wille, Gosia Trynka

Complex immune disease variants are enriched in active chromatin regions of T cells and macrophages. However, whether these variants function in specific cell states or stages of cell activation is unknown. We stimulated T cells and macrophages in the presence of thirteen different cytokine cocktails linked to immune diseases and profiled active enhancers and promoters together with regions of open chromatin. We observed that T cell activation induced major chromatin remodelling, while additional exposure to cytokines fine-tuned the magnitude of these changes. Therefore, we developed a new statistical method that accounts for subtle changes in chromatin landscape to identify SNP enrichment across cell states. Our results point towards the role of immune disease variants in early rather than late activation of memory CD4+ T cells, and with limited differences across polarizing cytokines. Furthermore, we demonstrate that inflammatory bowel disease variants are enriched in chromatin regions active in Th1 cells, while asthma variants overlap regions active in Th2 cells. We also show that Alzheimer’s disease variants are enriched in different macrophage cell states. Our results represent the first in-depth analysis of immune disease variants across a comprehensive panel of activation states of T cells and macrophages.

iDeal ChIP-seq Kit for Histones

Share this article

March, 2019


Products used in this publication

  • ChIP kit icon
    iDeal ChIP-seq kit for Histones


  • Virtual ChIP workshop - January 18-19, 2022 or January 25-26, 2022
    Jan 18-Jan 26, 2022
  • Virtual DNA Methylation - January 18-19, 2022 or January 25-26, 2022
    Jan 18-Jan 26, 2022
  • Lausanne Genomics Days 2022
    Lausanne, Switzerland
    Feb 14-Feb 15, 2022
 See all events


 See all news

The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.

       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics