TY  - JOUR
AU  - Chang, Yinshui
AU  - Bach, Luisa
AU  - Hasiuk, Marko
AU  - Wen, Lifen
AU  - Elmzzahi, Tarek
AU  - Tsui, Carlson
AU  - Gutiérrez-Melo, Nicolás
AU  - Steffen, Teresa
AU  - Utzschneider, Daniel T
AU  - Raj, Timsse
AU  - Jost, Paul Jonas
AU  - Heink, Sylvia
AU  - Cheng, Jingyuan
AU  - Burton, Oliver T
AU  - Zeiträg, Julia
AU  - Alterauge, Dominik
AU  - Dahlström, Frank
AU  - Becker, Jennifer-Christin
AU  - Kastl, Melanie
AU  - Symeonidis, Konstantinos
AU  - van Uelft, Martina
AU  - Becker, Matthias Kai Holger
AU  - Reschke, Sarah
AU  - Krebs, Stefan
AU  - Blum, Helmut
AU  - Abdullah, Zeinab
AU  - Paeschke, Katrin
AU  - Ohnmacht, Caspar
AU  - Neumann, Christian
AU  - Liston, Adrian
AU  - Meissner, Felix
AU  - Korn, Thomas
AU  - Hasenauer, Jan
AU  - Heissmeyer, Vigo
AU  - Beyer, Marc-Daniel
AU  - Kallies, Axel
AU  - Jeker, Lukas T
AU  - Baumjohann, Dirk
TI  - TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf.
JO  - Science immunology
VL  - 9
IS  - 93
SN  - 2470-9468
CY  - Washington, DC
PB  - AAAS
M1  - DZNE-2024-00239
SP  - eadd4818
PY  - 2024
AB  - 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.
KW  - Animals
KW  - Mice
KW  - T-Lymphocytes, Helper-Inducer
KW  - Transforming Growth Factor beta: metabolism
KW  - B-Lymphocytes
KW  - CD4-Positive T-Lymphocytes
KW  - Cell Differentiation
KW  - Proto-Oncogene Proteins c-maf: metabolism
KW  - Transforming Growth Factor beta (NLM Chemicals)
KW  - Maf protein, mouse (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-maf (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38427718
DO  - DOI:10.1126/sciimmunol.add4818
UR  - https://pub.dzne.de/record/268493
ER  -