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TCF-1 limits the formation of Tc17 cells via repression of the MAF-RORγt axis.
Mielke, Lisa A; Liao, Yang; Clemens, Ella Bridie; Firth, Matthew A; Duckworth, Brigette; Huang, Qiutong; Almeida, Francisca F; Chopin, Michael; Koay, Hui-Fern; Bell, Carolyn A; Hediyeh-Zadeh, Soroor; Park, Simone L; Raghu, Dinesh; Choi, Jarny; Putoczki, Tracy L; Hodgkin, Philip D; Franks, Ashley E; Mackay, Laura K; Godfrey, Dale I; Davis, Melissa J; Xue, Hai-Hui; Bryant, Vanessa L; Kedzierska, Katherine; Shi, Wei; Belz, Gabrielle T.
Afiliación
  • Mielke LA; Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Liao Y; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Clemens EB; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Australia.
  • Firth MA; Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Duckworth B; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Huang Q; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Almeida FF; Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Chopin M; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Koay HF; Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Bell CA; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Hediyeh-Zadeh S; Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Park SL; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Raghu D; Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Choi J; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Putoczki TL; Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Hodgkin PD; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Franks AE; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Mackay LK; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia.
  • Godfrey DI; Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Australia.
  • Davis MJ; Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Xue HH; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Bryant VL; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Australia.
  • Kedzierska K; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Australia.
  • Shi W; Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Belz GT; Department of Medical Biology, University of Melbourne, Parkville, Australia.
J Exp Med ; 216(7): 1682-1699, 2019 07 01.
Article en En | MEDLINE | ID: mdl-31142588
ABSTRACT
Interleukin (IL)-17-producing CD8+ T (Tc17) cells have emerged as key players in host-microbiota interactions, infection, and cancer. The factors that drive their development, in contrast to interferon (IFN)-γ-producing effector CD8+ T cells, are not clear. Here we demonstrate that the transcription factor TCF-1 (Tcf7) regulates CD8+ T cell fate decisions in double-positive (DP) thymocytes through the sequential suppression of MAF and RORγt, in parallel with TCF-1-driven modulation of chromatin state. Ablation of TCF-1 resulted in enhanced Tc17 cell development and exposed a gene set signature to drive tissue repair and lipid metabolism, which was distinct from other CD8+ T cell subsets. IL-17-producing CD8+ T cells isolated from healthy humans were also distinct from CD8+IL-17- T cells and enriched in pathways driven by MAF and RORγt Overall, our study reveals how TCF-1 exerts central control of T cell differentiation in the thymus by normally repressing Tc17 differentiation and promoting an effector fate outcome.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Interleucina-17 / Proteínas Proto-Oncogénicas c-maf / Factor Nuclear 1-alfa del Hepatocito / Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Exp Med Año: 2019 Tipo del documento: Article País de afiliación: Australia
Texto completo
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XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Interleucina-17 / Proteínas Proto-Oncogénicas c-maf / Factor Nuclear 1-alfa del Hepatocito / Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Exp Med Año: 2019 Tipo del documento: Article País de afiliación: Australia