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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 TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf.

Sci. Immunol. 9:eadd4818 (2024)
Verlagsversion DOI PMC
T follicular helper (TFH) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse TFH 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 TFH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4+ T cells in vitro. TGF-β-induced mouse CXCR5+ TFH cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated TFH 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 (TH17)-inducing conditions also yield separate CXCR5+ and IL-17A-producing cells, highlighting shared and distinct cell fate trajectories of TFH and TH17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-β-induced TFH cell program, that TFH and TH17 cells share a common developmental stage, and that c-Maf acts as a switch factor for TFH versus TH17 cell fates in TGF-β-rich environments in vitro and in vivo.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Follicular-helper-cells; Transcription Factor; Highly Efficient; Bcl6 Expression; In-vivo; B-cells; Differentiation; Gene; Il-21; Generation
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 2470-9468
e-ISSN 2470-9468
Zeitschrift Science immunology
Quellenangaben Band: 9, Heft: 93, Seiten: , Artikelnummer: eadd4818 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Allergy Research (IAF)
Institute of Computational Biology (ICB)
Research Unit Molecular Immune Regulation (AMIR)
POF Topic(s) 30202 - Environmental Health
30205 - Bioengineering and Digital Health
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Allergy
Enabling and Novel Technologies
Immune Response and Infection
PSP-Element(e) G-505400-001
G-553800-001
G-501712-001
Förderungen 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)
DOI 10.1126/sciimmunol.add4818
WOS ID 001186261800003
PubMed ID 38427718
Erfassungsdatum 2024-04-29
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