TGF-β specifies T FH versus T H 17 cell fates in murine CD4 + T cells through c-Maf.

Autor: Chang Y; Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.; Institute for Immunology, Faculty of Medicine, Biomedical Center, LMU Munich, Grosshaderner Str. 9, 82152 Planegg-Martinsried, Germany., Bach L; Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany., Hasiuk M; Department of Biomedicine, Basel University Hospital and University of Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.; Transplantation Immunology and Nephrology, Basel University Hospital, Petersgraben 4, CH-4031 Basel, Switzerland., Wen L; The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia., Elmzzahi T; The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.; Immunogenomics and Neurodegeneration, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany., Tsui C; The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia., Gutiérrez-Melo N; Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany., Steffen T; Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany., Utzschneider DT; The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia., Raj T; Institute for Immunology, Faculty of Medicine, Biomedical Center, LMU Munich, Grosshaderner Str. 9, 82152 Planegg-Martinsried, Germany., Jost PJ; Faculty of Mathematics and Natural Sciences, University of Bonn, Bonn, Germany., Heink S; Institute for Experimental Neuroimmunology, Technical University of Munich School of Medicine, 81675 Munich, Germany., Cheng J; Experimental Systems Immunology, Max Planck Institute of Biochemistry, Martinsried, Germany., Burton OT; Department of Pathology, University of Cambridge, Cambridge, UK., Zeiträg J; Institute for Immunology, Faculty of Medicine, Biomedical Center, LMU Munich, Grosshaderner Str. 9, 82152 Planegg-Martinsried, Germany., Alterauge D; Institute for Immunology, Faculty of Medicine, Biomedical Center, LMU Munich, Grosshaderner Str. 9, 82152 Planegg-Martinsried, Germany., Dahlström F; Institute for Immunology, Faculty of Medicine, Biomedical Center, LMU Munich, Grosshaderner Str. 9, 82152 Planegg-Martinsried, Germany., Becker JC; Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany., Kastl M; Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.; Department of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany., Symeonidis K; Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany., van Uelft M; Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany., Becker M; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.; PRECISE Platform for Single Cell Genomics and Epigenomics, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) and the University of Bonn, Bonn, Germany., Reschke S; Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str. 25, 81377 Munich, Germany., Krebs S; Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str. 25, 81377 Munich, Germany., Blum H; Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str. 25, 81377 Munich, Germany., Abdullah Z; Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany., Paeschke K; Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.; Department of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany., Ohnmacht C; Center of Allergy and Environment (ZAUM), Technical University and Helmholtz Center Munich, Munich, Germany., Neumann C; Department of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Liston A; Department of Pathology, University of Cambridge, Cambridge, UK., Meissner F; Experimental Systems Immunology, Max Planck Institute of Biochemistry, Martinsried, Germany.; Department of Systems Immunology and Proteomics, Institute of Innate Immunity, Medical Faculty, University of Bonn, Germany., Korn T; Institute for Experimental Neuroimmunology, Technical University of Munich School of Medicine, 81675 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany., Hasenauer J; Faculty of Mathematics and Natural Sciences, University of Bonn, Bonn, Germany.; Center for Mathematics, Technical University of Munich, Garching, Germany.; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany., Heissmeyer V; Institute for Immunology, Faculty of Medicine, Biomedical Center, LMU Munich, Grosshaderner Str. 9, 82152 Planegg-Martinsried, Germany.; Research Unit Molecular Immune Regulation, Helmholtz Zentrum München, Feodor-Lynen-Str. 21, 81377 Munich, Germany., Beyer M; Immunogenomics and Neurodegeneration, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.; PRECISE Platform for Single Cell Genomics and Epigenomics, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) and the University of Bonn, Bonn, Germany., Kallies A; The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia., Jeker LT; Department of Biomedicine, Basel University Hospital and University of Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.; Transplantation Immunology and Nephrology, Basel University Hospital, Petersgraben 4, CH-4031 Basel, Switzerland., Baumjohann D; Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.; Institute for Immunology, Faculty of Medicine, Biomedical Center, LMU Munich, Grosshaderner Str. 9, 82152 Planegg-Martinsried, Germany.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2024 Mar; Vol. 9 (93), pp. eadd4818. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.1126/sciimmunol.add4818
Abstrakt: T follicular helper (T FH ) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse T FH 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 T FH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4 + T cells in vitro. TGF-β-induced mouse CXCR5 + T FH cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated T FH 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 (T H 17)-inducing conditions also yield separate CXCR5 + and IL-17A-producing cells, highlighting shared and distinct cell fate trajectories of T FH and T H 17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-β-induced T FH cell program, that T FH and T H 17 cells share a common developmental stage, and that c-Maf acts as a switch factor for T FH versus T H 17 cell fates in TGF-β-rich environments in vitro and in vivo.
Databáze: MEDLINE