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Plasticity and lineage commitment of individual TH1 cells are determined by stable T-bet expression quantities

T helper 1 (TH1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated TH1 cells based on their quantitative...

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Main Authors: Hegazy, Ahmed Nabil (Author) , Peine, Caroline (Author) , Niesen, Dominik (Author) , Panse, Isabel (Author) , Vainshtein, Yevhen (Author) , Kommer, Christoph (Author) , Zhang, Qin (Author) , Brunner, Tobias M. (Author) , Peine, Michael (Author) , Fröhlich, Anja (Author) , Ishaque, Naveed (Author) , Marek, Roman M. (Author) , Zhu, Jinfang (Author) , Höfer, Thomas (Author) , Löhning, Max (Author)
Format: Article (Journal)
Language:English
Published: June 7, 2024
In: Science advances
Year: 2024, Volume: 10, Issue: 23, Pages: 1-15
ISSN:2375-2548
DOI:10.1126/sciadv.adk2693
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1126/sciadv.adk2693
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Author Notes:Ahmed N. Hegazy, Caroline Peine, Dominik Niesen, Isabel Panse, Yevhen Vainshtein, Christoph Kommer, Qin Zhang, Tobias M. Brunner, Michael Peine, Anja Fröhlich, Naveed Ishaque, Roman M. Marek, Jinfang Zhu, Thomas Höfer, Max Löhning
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Summary:T helper 1 (TH1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated TH1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type I interferons and were stably maintained even after secondary viral infection. Exposed to alternative differentiation signals, the sorted subpopulations exhibited graded levels of plasticity, particularly toward the TH2 lineage: T-bet quantities were inversely correlated with the ability to express the TH2 lineage-specifying transcription factor GATA-3 and TH2 cytokines. Reprogramed TH1 cells acquired graded mixed TH1 + TH2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated TH1 cells was essential to ensure TH1 cell stability. Thus, innate cytokine signals regulate TH1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges.
Item Description:Gesehen am 14.02.2025
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Physical Description:Online Resource
ISSN:2375-2548
DOI:10.1126/sciadv.adk2693

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