A unified network systems approach uncovers a core program underlying T follicular helper cell differentiation
Year: 2026
Type: article
Abstract: 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/. Follicular helper T (TFH) cells are functionally diverse and plastic. Here, using a multi-scale approach integrating multi-omic data with regulatory and protein networks, the authors present a core gene network involved in TFH differentiation, which is conserved across species, tissues and disease.
Source: Nature Communications
Authors: 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
Institutions: University of Pittsburgh, Carnegie Mellon University, Harvard University, Ragon Institute of MGH, MIT and Harvard, Northwell Health, Feinstein Institute for Medical Research, Emory University, Ghent University Hospital, Ghent University, Brigham and Women's Hospital, Instituto Nacional de Enfermedades Respiratorias
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7170064700