Journal Article

DZNE-2024-00239

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf.

Chang, Y. ; Bach, L. ; Hasiuk, M. ; Wen, L. ; Elmzzahi, T.DZNE* ; 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.Extern* ; Becker, M. K. H.DZNE* ; 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.-D.DZNE* ; Kallies, A. ; Jeker, L. T. ; Baumjohann, D.

2024
AAAS Washington, DC

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Please use a persistent id in citations: doi:10.1126/sciimmunol.add4818

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.

Keyword(s): Animals (MeSH) ; Mice (MeSH) ; T-Lymphocytes, Helper-Inducer (MeSH) ; Transforming Growth Factor beta: metabolism (MeSH) ; B-Lymphocytes (MeSH) ; CD4-Positive T-Lymphocytes (MeSH) ; Cell Differentiation (MeSH) ; Proto-Oncogene Proteins c-maf: metabolism (MeSH) ; Transforming Growth Factor beta ; Maf protein, mouse ; Proto-Oncogene Proteins c-maf

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Contributing Institute(s):

1. Immunogenomics and Neurodegeneration (AG Beyer)
2. Modular High Performance Computing and Artificial Intelligence (AG Becker)
3. Platform for Single Cell Genomics and Epigenomics (PRECISE)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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