Divergent cytokine and transcriptional signatures control functional T follicular helper cell heterogeneity

Dalit, L; Tan, CW; Sheikh, AA; Munnings, R; Howson, LJ; Alvarado, C; Hussain, T; Zaini, A; Cooper, L; Kirn, A; Hailes, L; Nguyen, A; Williams, BE; Zheng, MZM; van de Sandt, CE; Mackay, LK; Flanagan, KL; Kedzierska, K; Harris, N; Juno, JA; Zaph, C; La Gruta, NL; Davis, MJ; Nutt, SL; Good-Jacobson, KL; Bryant, VL; Groom, JR

Author(s): Dalit, L; Tan, CW; Sheikh, AA; Munnings, R; Howson, LJ; Alvarado, C; Hussain, T; Zaini, A; Cooper, L; Kirn, A; Hailes, L; Nguyen, A; Williams, BE; Zheng, MZM; van de Sandt, CE; Mackay, LK; Flanagan, KL; Kedzierska, K; Harris, N; Juno, JA; Zaph, C; La Gruta, NL; Davis, MJ; Nutt, SL; Good-Jacobson, KL; Bryant, VL; Groom, JR;
Details: Publication Year 2025-10,Volume 26,Issue #10,Page 1821-1835
Journal Title: Nature Immunology
Abstract: CD4(+) T follicular helper (T(FH)) cells support tailored B cell responses against multiple classes of pathogens. To reveal how diverse T(FH) phenotypes are established, we profiled mouse T(FH) cells in response to viral, helminth and bacterial infection. We identified a core T(FH) signature that is distinct from CD4(+) T follicular regulatory and effector cells and identified pathogen-specific transcriptional modules that shape T(FH) function. Cytokine-transcriptional T(FH) programming demonstrated that type I interferon and TGFbeta signaling direct individual T(FH) phenotypes to instruct B cell output. Cytokine-directed T(FH) transcriptional phenotypes are shared within human germinal centers, but distinct T(FH) phenotypes dominate between donors and following immune challenge or in antibody-mediated disease. Finally, we identified new cell surface markers that align with distinct T(FH) phenotypes. Thus, we provide a comprehensive resource of T(FH) diversity in humans and mice to enable immune monitoring during infection and disease and to inform the development of context-specific vaccines.
Publisher: Springer Nature
Keywords: Animals; Mice; *T Follicular Helper Cells/immunology/metabolism; Humans; *Cytokines/metabolism/immunology; Germinal Center/immunology; B-Lymphocytes/immunology; Mice, Inbred C57BL; Transforming Growth Factor beta/metabolism; Transcriptome; Signal Transduction; *T-Lymphocytes, Helper-Inducer/immunology
Research Division(s): Immunology; Bioinformatics and Computational Biology
PubMed ID: 40926076
Publisher's Version: https://doi.org/10.1038/s41590-025-02258-9
Open Access at Publisher's Site: https://doi.org/10.1038/s41590-025-02258-9
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-09-23 08:17:29

Last Modified: 2025-10-20 01:59:38