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@ARTICLE{Chang:268493,
author = {Chang, Yinshui and Bach, Luisa and Hasiuk, Marko and Wen,
Lifen and Elmzzahi, Tarek and Tsui, Carlson and
Gutiérrez-Melo, Nicolás and Steffen, Teresa and
Utzschneider, Daniel T and Raj, Timsse and Jost, Paul Jonas
and Heink, Sylvia and Cheng, Jingyuan and Burton, Oliver T
and Zeiträg, Julia and Alterauge, Dominik and Dahlström,
Frank and Becker, Jennifer-Christin and Kastl, Melanie and
Symeonidis, Konstantinos and van Uelft, Martina and Becker,
Matthias Kai Holger and Reschke, Sarah and Krebs, Stefan and
Blum, Helmut and Abdullah, Zeinab and Paeschke, Katrin and
Ohnmacht, Caspar and Neumann, Christian and Liston, Adrian
and Meissner, Felix and Korn, Thomas and Hasenauer, Jan and
Heissmeyer, Vigo and Beyer, Marc-Daniel and Kallies, Axel
and Jeker, Lukas T and Baumjohann, Dirk},
title = {{TGF}-β specifies {TFH} versus {TH}17 cell fates in murine
{CD}4+ {T} cells through c-{M}af.},
journal = {Science immunology},
volume = {9},
number = {93},
issn = {2470-9468},
address = {Washington, DC},
publisher = {AAAS},
reportid = {DZNE-2024-00239},
pages = {eadd4818},
year = {2024},
abstract = {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.},
keywords = {Animals / Mice / T-Lymphocytes, Helper-Inducer /
Transforming Growth Factor beta: metabolism / B-Lymphocytes
/ CD4-Positive T-Lymphocytes / Cell Differentiation /
Proto-Oncogene Proteins c-maf: metabolism / Transforming
Growth Factor beta (NLM Chemicals) / Maf protein, mouse (NLM
Chemicals) / Proto-Oncogene Proteins c-maf (NLM Chemicals)},
cin = {AG Beyer / AG Becker / PRECISE},
ddc = {610},
cid = {I:(DE-2719)1013035 / I:(DE-2719)5000079 /
I:(DE-2719)1013031},
pnm = {351 - Brain Function (POF4-351) / 354 - Disease Prevention
and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-354},
experiment = {EXP:(DE-2719)PRECISE-20190321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38427718},
doi = {10.1126/sciimmunol.add4818},
url = {https://pub.dzne.de/record/268493},
}