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<p>Characterizing multi-scale processes underlying immune-state progression is critical for defining their function. This becomes pertinent for functionally diverse and plastic immune cells, such as T follicular helper (Tfh) cells. Here, we adopt a multi-scale network-systems approach that incorporates both regulatory and protein-protein interactions. This approach integrates diverse data types, captures regulation across levels of immune system organization, and recapitulates known Tfh differentiation drivers. Further, we present CoreNet, a core Tfh gene set that is conserved between humans and mice, across tissue types and disease contexts, and is consistent across data modalities. Using CoreNet, we implicate NR3C1 and interleukin (IL)-12 in the regulation of Tfh differentiation. Notably, IL-12 is permissive for differentiation of Tfh precursors but blocks differentiation into germinal center Tfh cells. Overall, this work elucidates networks with unexplored roles governing Tfh differentiation across species and tissues, while providing a generalizable framework. CoreNet is accessible through an interactive web server: <a href="https://pitt-csi.shinyapps.io/tfhcorenet/">https://pitt-csi.shinyapps.io/tfhcorenet/</a>.</p>

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A unified network systems approach uncovers a core program underlying T follicular helper cell differentiation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月22日

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  • Alisa A. Omelchenko,
  • Syed A. Rahman,
  • Alyson Wang,
  • Tracy Tabib,
  • Vinayak V. Viswanadham,
  • Grace J. Yuen,
  • Perla M. Del Rio Estrada,
  • Valentino D’Onofrio,
  • Yijia Chen,
  • Na Sun,
  • Hamid Mattoo,
  • Swapnil Keshari,
  • Chinmay V. Gadiraju,
  • Gonzalo Salgado,
  • Maribel Soto-Nava,
  • Lady Ruiz-Carbajal,
  • Dafne Díaz-Rivera,
  • Santiago Ávila-Ríos,
  • Sudhir P. Kasturi,
  • Susan P. Ribeiro,
  • Mark J. Shlomchik,
  • Amanda C. Poholek,
  • Shiv Pillai,
  • Rebecca A. Elsner,
  • Vinay S. Mahajan,
  • Jishnu Das

摘要

Characterizing multi-scale processes underlying immune-state progression is critical for defining their function. This becomes pertinent for functionally diverse and plastic immune cells, such as T follicular helper (Tfh) cells. Here, we adopt a multi-scale network-systems approach that incorporates both regulatory and protein-protein interactions. This approach integrates diverse data types, captures regulation across levels of immune system organization, and recapitulates known Tfh differentiation drivers. Further, we present CoreNet, a core Tfh gene set that is conserved between humans and mice, across tissue types and disease contexts, and is consistent across data modalities. Using CoreNet, we implicate NR3C1 and interleukin (IL)-12 in the regulation of Tfh differentiation. Notably, IL-12 is permissive for differentiation of Tfh precursors but blocks differentiation into germinal center Tfh cells. Overall, this work elucidates networks with unexplored roles governing Tfh differentiation across species and tissues, while providing a generalizable framework. CoreNet is accessible through an interactive web server: https://pitt-csi.shinyapps.io/tfhcorenet/.