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Chang, Y.* ; Bach, L.* ; Hasiuk, M.* ; Wen, L.* ; Elmzzahi, T.* ; Tsui, C.* ; Gutiérrez-Melo, N.* ; Steffen, T.* ; Utzschneider, D.T.* ; Raj, T.* ; Jost, P.J.* ; Heink, S.* ; Cheng, J.* ; Burton, O.T.* ; Zeiträg, J.* ; Alterauge, D.* ; Dahlström, F.* ; Becker, J.C.* ; Kastl, M.* ; Symeonidis, K.* ; van Uelft, M.* ; Becker, M.* ; Reschke, S.* ; Krebs, S.* ; Blum, H.* ; Abdullah, Z.* ; Paeschke, K.* ; Ohnmacht, C. ; Neumann, C.* ; Liston, A.* ; Meissner, F.* ; Korn, T.* ; Hasenauer, J. ; Heissmeyer, V. ; Beyer, M.* ; Kallies, A.* ; Jeker, L.T.* ; Baumjohann, D.*

TGF-β specifies T_FH versus T_H17 cell fates in murine CD4⁺ T cells through c-Maf.

Sci. Immunol. 9:eadd4818 (2024)

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T follicular helper (T_FH) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse T_FH cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor-β (TGF-β) induces robust expression of T_FH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4⁺ T cells in vitro. TGF-β-induced mouse CXCR5⁺ T_FH cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated T_FH cells and provide critical help to B cells. The study further reveals that TGF-β-induced CXCR5 expression is independent of Bcl6 but requires the transcription factor c-Maf. Classical TGF-β-containing T helper 17 (T_H17)-inducing conditions also yield separate CXCR5⁺ and IL-17A-producing cells, highlighting shared and distinct cell fate trajectories of T_FH and T_H17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-β-induced T_FH cell program, that T_FH and T_H17 cells share a common developmental stage, and that c-Maf acts as a switch factor for T_FH versus T_H17 cell fates in TGF-β-rich environments in vitro and in vivo.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Follicular-helper-cells; Transcription Factor; Highly Efficient; Bcl6 Expression; In-vivo; B-cells; Differentiation; Gene; Il-21; Generation

ISSN (print) / ISBN 2470-9468

e-ISSN 2470-9468

Journal Science immunology

Quellenangaben Volume: 9, Issue: 93, Article Number: eadd4818

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place Washington, DC

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute for Allergy Research (IAF)
Institute of Computational Biology (ICB)
Abteilung für Molekulare Immunregulation (AMIR)

Grants Ministry of Culture and Science of the State of northrhine Westphalia
DFG
State government
Ministry of Culture and Science of the State of North Rhine-Westphalia (MKW) as part of Strategy of the Federal government
Federal Ministry of Education and Research (BMBF)
University of Bonn
University of Melbourne
IMuexcellent
Germany's excellence Strategy
Hertie Network of Clinical Neuroscience
Wellcome Trust
ERC
Basel University Hospital
European Research Council (ERC)
Swiss National Science Foundation (SNSF)
Krebshilfe foundations
Else Kroener- Fresenius
Wilhelm Sander
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)