RORγt+ c-Maf+ Vγ4+ γδ T cells are generated in the adult thymus but do not reach the periphery
Tao Yang,
Joana Barros-Martins,
Ziqing Wang,
Melanie Wencker,
Jiang Zhang,
Justine Smout,
Prerna Gambhir,
Anika Janssen,
Anja Schimrock,
Hristo Georgiev,
Ximena León-Lara,
Siegfried Weiss,
Jochen Huehn,
Immo Prinz,
Andreas Krueger,
Reinhold Foerster,
Thierry Walzer,
Sarina Ravens
Affiliations
Tao Yang
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany
Joana Barros-Martins
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany
Ziqing Wang
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany
Melanie Wencker
Centre International de Recherche en Infectiologie, INSERM U1111, École Normale Supérieure de Lyon, Claude Bernard University Lyon 1, CNRS, UMR 5308, 69365 Lyon, France
Jiang Zhang
Centre International de Recherche en Infectiologie, INSERM U1111, École Normale Supérieure de Lyon, Claude Bernard University Lyon 1, CNRS, UMR 5308, 69365 Lyon, France
Justine Smout
Experimental Immunology, Helmholtz Centre for Infection Research, 39124 Braunschweig, Germany
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany
Anja Schimrock
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany
Hristo Georgiev
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany
Ximena León-Lara
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany
Siegfried Weiss
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, 30625 Hannover, Germany
Jochen Huehn
Experimental Immunology, Helmholtz Centre for Infection Research, 39124 Braunschweig, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, 30625 Hannover, Germany
Immo Prinz
Institute of Systems Immunology, University Hamburg-Eppendorf, 20246 Hamburg, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, 30625 Hannover, Germany
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, 30625 Hannover, Germany
Thierry Walzer
Centre International de Recherche en Infectiologie, INSERM U1111, École Normale Supérieure de Lyon, Claude Bernard University Lyon 1, CNRS, UMR 5308, 69365 Lyon, France
Sarina Ravens
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, 30625 Hannover, Germany; Corresponding author
Summary: T cell receptor (TCR) Vγ4-expressing γδ T cells comprise interferon γ (IFNγ)- and interleukin-17 (IL-17)-producing effector subsets, with a preference for IL-17 effector fate decisions during early ontogeny. The existence of adult-thymus-derived IL-17+ T cells (γδ17) remains controversial. Here, we use a mouse model in which T cells are generated exclusively in the adult thymus and employ single-cell chromatin state analysis to study their development. We identify adult-thymus-derived Vγ4 T cells that have all the molecular programs to become IL-17 producers. However, they have reduced IL-17 production capabilities and rarely reach the periphery. Moreover, this study provides high-resolution profiles of Vγ4 T cells in the adult thymus and lymph nodes and identifies Zeb1 as a potential γδ17 cell regulator. Together, this study provides valuable insights into the developmental traits of Vγ4 T cells during adulthood and supports the idea of age-specific signals required for thymic export and/or peripheral maturation of γδ17 cells.
