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<p>Genetic and immunologic studies implicate the interleukin (IL)-23/T helper (Th)17 pathway in inflammatory bowel disease (IBD). IL-23 and IL-1β drive human Th17 differentiation, while prostaglandin E2 (PGE<sub>2</sub>) and transforming growth factor-β (TGF-β) further modulate Th17 development and plasticity. However, how these inflammatory mediators influence human T cell regulatory programs remains incompletely understood. We used single-cell multi-omics to profile 171,829 peripheral blood T cells from 25 healthy donors in 64 samples exposed to activation stimuli, IL-1β and IL-23 alone or in combination with PGE<sub>2</sub>, TGF-β, or both. PGE<sub>2</sub> broadly suppressed T cell activation, except in Th17 and T follicular helper cells, and markedly altered chromatin accessibility and gene expression, particularly in Th17, Th1, and regulatory T cells, where IBD-associated SNPs were enriched in open chromatin and connected to cell type-specific cis-regulatory elements. Our study demonstrates the utility of single-cell multi-omics for defining stimulus-specific effects on T cells and prioritizing disease-associated genes.</p>

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Dissecting PGE2-driven inhibition of T cell activation using single-cell multi-omic and inflammatory bowel disease genetic association analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月7日

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  • Zhongli Xu,
  • Shiyue Tao,
  • Site Feng,
  • Xiangyu Ye,
  • Ting Wang,
  • Haoran Hu,
  • Elisa Heidrich-O’Hare,
  • Wei Chen,
  • Richard H. Duerr

摘要

Genetic and immunologic studies implicate the interleukin (IL)-23/T helper (Th)17 pathway in inflammatory bowel disease (IBD). IL-23 and IL-1β drive human Th17 differentiation, while prostaglandin E2 (PGE2) and transforming growth factor-β (TGF-β) further modulate Th17 development and plasticity. However, how these inflammatory mediators influence human T cell regulatory programs remains incompletely understood. We used single-cell multi-omics to profile 171,829 peripheral blood T cells from 25 healthy donors in 64 samples exposed to activation stimuli, IL-1β and IL-23 alone or in combination with PGE2, TGF-β, or both. PGE2 broadly suppressed T cell activation, except in Th17 and T follicular helper cells, and markedly altered chromatin accessibility and gene expression, particularly in Th17, Th1, and regulatory T cells, where IBD-associated SNPs were enriched in open chromatin and connected to cell type-specific cis-regulatory elements. Our study demonstrates the utility of single-cell multi-omics for defining stimulus-specific effects on T cells and prioritizing disease-associated genes.