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Plasticity and lineage commitment of individual TH1 cells are determined by stable T-bet expression quantities.
Hegazy, Ahmed N; Peine, Caroline; Niesen, Dominik; Panse, Isabel; Vainshtein, Yevhen; Kommer, Christoph; Zhang, Qin; Brunner, Tobias M; Peine, Michael; Fröhlich, Anja; Ishaque, Naveed; Marek, Roman M; Zhu, Jinfang; Höfer, Thomas; Löhning, Max.
Afiliación
  • Hegazy AN; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medical Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany.
  • Peine C; German Rheumatism Research Center (DRFZ), a Leibniz Institute, Inflammatory Mechanisms, 10117 Berlin, Germany.
  • Niesen D; Berlin Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
  • Panse I; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental Immunology and Osteoarthritis Research, Department of Rheumatology and Clinical Immunology, 10117 Berlin, Germany.
  • Vainshtein Y; German Rheumatism Research Center (DRFZ), a Leibniz Institute, Pitzer Laboratory of Osteoarthritis Research, 10117 Berlin, Germany.
  • Kommer C; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental Immunology and Osteoarthritis Research, Department of Rheumatology and Clinical Immunology, 10117 Berlin, Germany.
  • Zhang Q; German Rheumatism Research Center (DRFZ), a Leibniz Institute, Pitzer Laboratory of Osteoarthritis Research, 10117 Berlin, Germany.
  • Brunner TM; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental Immunology and Osteoarthritis Research, Department of Rheumatology and Clinical Immunology, 10117 Berlin, Germany.
  • Peine M; German Rheumatism Research Center (DRFZ), a Leibniz Institute, Pitzer Laboratory of Osteoarthritis Research, 10117 Berlin, Germany.
  • Fröhlich A; German Cancer Research Center (DKFZ), Division of Theoretical Systems Biology, 69120 Heidelberg, Germany.
  • Ishaque N; University of Heidelberg, Bioquant Center, 69120 Heidelberg, Germany.
  • Marek RM; German Cancer Research Center (DKFZ), Division of Theoretical Systems Biology, 69120 Heidelberg, Germany.
  • Zhu J; University of Heidelberg, Bioquant Center, 69120 Heidelberg, Germany.
  • Höfer T; German Cancer Research Center (DKFZ), Division of Theoretical Systems Biology, 69120 Heidelberg, Germany.
  • Löhning M; University of Heidelberg, Bioquant Center, 69120 Heidelberg, Germany.
Sci Adv ; 10(23): eadk2693, 2024 Jun 07.
Article en En | MEDLINE | ID: mdl-38838155
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Células Th2 / Células TH1 / Linaje de la Célula / Proteínas de Dominio T Box / Plasticidad de la Célula Límite: Animals Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Células Th2 / Células TH1 / Linaje de la Célula / Proteínas de Dominio T Box / Plasticidad de la Célula Límite: Animals Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos