Plasticity and lineage commitment of individual Th1 cells are determined by stable T-bet expression quantities
SUMMARY T helper 1 (Th1) cell identity is defined by the expression of the lineage-defining transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinctin 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 Th2-polarizing conditions, the sorted subpopulations exhibited graded levels of plasticity: 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, but stable mixed Th1+2 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.HIGHLIGHTS <jats:list list-type="bullet">Type-I interferons triggered by infection determine T-bet expression states in Th1 cellsT-bet and IFN-γ expression states indicate the plasticity of individual Th1 cellsIndividual T-bet expression states and plasticity persist after secondary infectionReprogramming yields stable Th1+2 phenotypes and a mixed epigenetic landscape.
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 14. Feb. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hegazy, Ahmed N. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2022.08.14.503916 |
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| PPN (Katalog-ID): |
XBI036861650 |
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| 100 | 1 | |a Hegazy, Ahmed N. |e verfasserin |0 (orcid)0000-0002-2946-8251 |4 aut | |
| 245 | 1 | 0 | |a Plasticity and lineage commitment of individual Th1 cells are determined by stable T-bet expression quantities |
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| 520 | |a SUMMARY T helper 1 (Th1) cell identity is defined by the expression of the lineage-defining transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinctin 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 Th2-polarizing conditions, the sorted subpopulations exhibited graded levels of plasticity: 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, but stable mixed Th1+2 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.HIGHLIGHTS <jats:list list-type="bullet">Type-I interferons triggered by infection determine T-bet expression states in Th1 cellsT-bet and IFN-γ expression states indicate the plasticity of individual Th1 cellsIndividual T-bet expression states and plasticity persist after secondary infectionReprogramming yields stable Th1+2 phenotypes and a mixed epigenetic landscape | ||
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| 700 | 1 | |a Niesen, Dominik |4 aut | |
| 700 | 1 | |a Panse, Isabel |4 aut | |
| 700 | 1 | |a Vainshtein, Yevhen |4 aut | |
| 700 | 1 | |a Kommer, Christoph |4 aut | |
| 700 | 1 | |a Zhang, Qin |4 aut | |
| 700 | 1 | |a Brunner, Tobias M. |4 aut | |
| 700 | 1 | |a Peine, Michael |4 aut | |
| 700 | 1 | |a Fröhlich, Anja |4 aut | |
| 700 | 1 | |a Ishaque, Naveed |4 aut | |
| 700 | 1 | |a Marek, Roman M. |4 aut | |
| 700 | 1 | |a Zhu, Jinfang |4 aut | |
| 700 | 1 | |a Höfer, Thomas |0 (orcid)0000-0003-3560-8780 |4 aut | |
| 700 | 1 | |a Löhning, Max |4 aut | |
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