T-cell and B-cell Immunology
Open access
Peer reviewed
Scollr summary
What this paper is about
The findings establish the IL-6-C/EBPα axis as a critical mechanism driving Tfr differentiation to restrain pathogenic humoral immunity.
Full abstract
Read the full abstract
Follicular regulatory T (Tfr) cells maintain immune homeostasis by suppressing excessive germinal center (GC) responses. However, the molecular mechanisms governing Tfr differentiation remain incompletely understood. Here, we identify interleukin-6 (IL-6) as a key regulator of Tfr generation. IL-6/IL-6Rα signaling promotes the differentiation of regulatory T cells (Treg) into Tfr cells by inducing CCAAT/enhancer binding protein α (C/EBPα), which binds the Bcl6 and Cxcr5 promoters in Tfr cells. Treg-specific deletion of C/EBPα in mice impairs Tfr differentiation, resulting in hyperactive GC responses and exacerbated pathology in mouse models of systemic lupus erythematosus (SLE) and HDM-induced allergy. In humans, in silico perturbation of CEBPA in Tregs disrupts the Tfr differentiation trajectory. Furthermore, CEBPA expression in Tregs, but not total CD4+ T cells, from patients with SLE negatively correlates with disease activity (SLEDAI). Thus, these findings establish the IL-6–C/EBPα axis as a critical mechanism driving Tfr differentiation to restrain pathogenic humoral immunity. Follicular regulatory T cells (Tfr) contribute to the maintenance of humoral immune homeostasis by modulating aberrant germinal center (GC) activation. Cytokine signaling contributes to Tfr differentiation; however, the complete cytokine landscape regulating Tfr biology has yet to be determined. Here, the authors identify an IL-6-C/EBPα axis that drives Tfr cell differentiation via upregulation of Bcl6 and CXCR5 protein and show that the dysregulation of this axis alters Tfr-mediated suppression of B cell responses, exacerbating SLE pathology and allergic responses in mice.
Direct answer
What can I do from this paper page?
Use this page to scan "IL-6-induced C/EBPα drives follicular regulatory T cell differentiation to regulate humoral immunity in mice" quickly: start with the summary and abstract, then check the authors, source, topics, and related papers. From here, open Scollr to follow T-cell and B-cell Immunology research, save the paper, or map adjacent work.
Research areas
Follow related topics
Citation
BibTeX
@article{Lee2026induced,
title = {IL-6-induced C/EBPα drives follicular regulatory T cell differentiation to regulate humoral immunity in mice},
author = {H J Lee and Chan Johng Kim and Hyunsoo Ahn and Gayeon Cho and Sang-Hyeon Mun and S. Kim and Hyung-Seok Choi and Dahun Um and Hyeongseop Kim and Haeun Ko and Jun-Hee Noh and John Chulhoon Park and Hye Eun Park and Amit Sharma and Yoontae Lee and Seung‐Woo Lee and Youn Soo Choi and Chang‐Hee Suh and Jae‐Joong Kim and Tae-Kyung Kim and Cheol‐Sang Hwang and Jong Kim and Sanguk Kim and Sin‐Hyeog Im},
journal = {Nature Communications},
year = {2026},
doi = {10.1038/s41467-026-75308-x},
url = {https://doi.org/10.1038/s41467-026-75308-x}
}FAQ
Using this paper in a discovery workflow
How do I find related work for this paper?
Use the related papers and topic links on this page as starting points. In Scollr, you can also open the paper and build a literature map around its references, citing papers, and related work.
How can I keep up with new T-cell and B-cell Immunology research papers?
Follow T-cell and B-cell Immunology research in Scollr. New papers from the topic flow into a personalized feed, and you can save useful studies to revisit later.
Can I cite this paper from this page?
This page includes a static BibTeX block for IL-6-induced C/EBPα drives follicular regulatory T cell differentiation to regulate humoral immunity in mice. Always verify the DOI, source, and publication details against the publisher record before submitting a manuscript.
Follow this research in Scollr
Follow the topics and authors behind this paper, save useful studies, and build a literature map when you are ready to go deeper.
Get the app