Home > Publications Database > TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf. > print

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024 7 _ |a 10.1126/sciimmunol.add4818
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037 _ _ |a DZNE-2024-00239
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Chang, Yinshui
|0 0000-0003-3538-6663
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245 _ _ |a TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf.
260 _ _ |a Washington, DC
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520 _ _ |a 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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650 _ 7 |a Transforming Growth Factor beta
|2 NLM Chemicals
650 _ 7 |a Maf protein, mouse
|2 NLM Chemicals
650 _ 7 |a Proto-Oncogene Proteins c-maf
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a T-Lymphocytes, Helper-Inducer
|2 MeSH
650 _ 2 |a Transforming Growth Factor beta: metabolism
|2 MeSH
650 _ 2 |a B-Lymphocytes
|2 MeSH
650 _ 2 |a CD4-Positive T-Lymphocytes
|2 MeSH
650 _ 2 |a Cell Differentiation
|2 MeSH
650 _ 2 |a Proto-Oncogene Proteins c-maf: metabolism
|2 MeSH
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700 1 _ |a Bach, Luisa
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700 1 _ |a Hasiuk, Marko
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700 1 _ |a Wen, Lifen
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700 1 _ |a Elmzzahi, Tarek
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700 1 _ |a Tsui, Carlson
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700 1 _ |a Gutiérrez-Melo, Nicolás
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700 1 _ |a Steffen, Teresa
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700 1 _ |a Utzschneider, Daniel T
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700 1 _ |a Jost, Paul Jonas
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700 1 _ |a Heink, Sylvia
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700 1 _ |a Cheng, Jingyuan
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700 1 _ |a Burton, Oliver T
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700 1 _ |a Zeiträg, Julia
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700 1 _ |a Alterauge, Dominik
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700 1 _ |a Dahlström, Frank
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700 1 _ |a Becker, Jennifer-Christin
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700 1 _ |a Kastl, Melanie
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700 1 _ |a Symeonidis, Konstantinos
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700 1 _ |a van Uelft, Martina
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700 1 _ |a Becker, Matthias Kai Holger
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700 1 _ |a Reschke, Sarah
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700 1 _ |a Krebs, Stefan
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700 1 _ |a Blum, Helmut
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700 1 _ |a Abdullah, Zeinab
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700 1 _ |a Paeschke, Katrin
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700 1 _ |a Ohnmacht, Caspar
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700 1 _ |a Neumann, Christian
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700 1 _ |a Liston, Adrian
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700 1 _ |a Meissner, Felix
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700 1 _ |a Korn, Thomas
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700 1 _ |a Hasenauer, Jan
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700 1 _ |a Heissmeyer, Vigo
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700 1 _ |a Beyer, Marc-Daniel
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700 1 _ |a Kallies, Axel
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700 1 _ |a Jeker, Lukas T
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700 1 _ |a Baumjohann, Dirk
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773 _ _ |a 10.1126/sciimmunol.add4818
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