%0 Journal Article
%A Chang, Yinshui
%A Bach, Luisa
%A Hasiuk, Marko
%A Wen, Lifen
%A Elmzzahi, Tarek
%A Tsui, Carlson
%A Gutiérrez-Melo, Nicolás
%A Steffen, Teresa
%A Utzschneider, Daniel T
%A Raj, Timsse
%A Jost, Paul Jonas
%A Heink, Sylvia
%A Cheng, Jingyuan
%A Burton, Oliver T
%A Zeiträg, Julia
%A Alterauge, Dominik
%A Dahlström, Frank
%A Becker, Jennifer-Christin
%A Kastl, Melanie
%A Symeonidis, Konstantinos
%A van Uelft, Martina
%A Becker, Matthias Kai Holger
%A Reschke, Sarah
%A Krebs, Stefan
%A Blum, Helmut
%A Abdullah, Zeinab
%A Paeschke, Katrin
%A Ohnmacht, Caspar
%A Neumann, Christian
%A Liston, Adrian
%A Meissner, Felix
%A Korn, Thomas
%A Hasenauer, Jan
%A Heissmeyer, Vigo
%A Beyer, Marc-Daniel
%A Kallies, Axel
%A Jeker, Lukas T
%A Baumjohann, Dirk
%T TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf.
%J Science immunology
%V 9
%N 93
%@ 2470-9468
%C Washington, DC
%I AAAS
%M DZNE-2024-00239
%P eadd4818
%D 2024
%X 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.
%K Animals
%K Mice
%K T-Lymphocytes, Helper-Inducer
%K Transforming Growth Factor beta: metabolism
%K B-Lymphocytes
%K CD4-Positive T-Lymphocytes
%K Cell Differentiation
%K Proto-Oncogene Proteins c-maf: metabolism
%K Transforming Growth Factor beta (NLM Chemicals)
%K Maf protein, mouse (NLM Chemicals)
%K Proto-Oncogene Proteins c-maf (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38427718
%R 10.1126/sciimmunol.add4818
%U https://pub.dzne.de/record/268493