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Divergent cytokine and transcriptional signatures control functional T follicular helper cell heterogeneity (scRNAseq/CITEseq)

GSE302645 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/08/25 Platform GPL24676
Summary
CD4+ T follicular helper (Tfh) cells support tailored B cell responses against multiple classes of pathogens. To reveal how diverse Tfh phenotypes are established, we profiled Tfh cells in response to viral, helminth and bacterial infection. We identified a core Tfh signature that is distinct from CD4+ T follicular regulatory and effector cells and identified pathogen-specific transcriptional modules that shape Tfh function. Cytokine-transcriptional Tfh programming demonstrated that type I interferon and TGFbeta signaling direct individual Tfh phenotypes to instruct B cell output. Cytokine-directed Tfh transcriptional phenotypes are shared within human germinal centers (GCs), but distinct Tfh phenotypes dominate between donors and following immune challenge or in antibody-mediated disease. Finally, we identified novel cell surface markers that align with distinct Tfh phenotypes. Thus, we provide a comprehensive resource of Tfh diversity in humans and mice, to enable immune monitoring during infection and disease and to inform the development of context-specific vaccines.
Published in
Divergent cytokine and transcriptional signatures control functional T follicular helper cell heterogeneity
Dalit L, Tan CW, Sheikh AA et al. · Nature immunology 2025 · PMID 40926076 · doi:10.1038/s41590-025-02258-9
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Direct links to NCBI, no account and no request form: the whole study as GSE302645_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1291653 and SRA study SRP601072. Searching any of these in the dataset finder brings you back here.

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