Brief homogeneous TCR signals instruct common iNKT progenitors whose effector diversification is characterized by subsequent cytokine signaling
| Autor: | Thorsten Buch, Nyambayar Dashtsoodol, Tim Ammon, Sabine Helmrath, Roland Rad, Marc Schmidt-Supprian, Christoph Drees, Rupert Öllinger, Thomas Engleitner, Maria Solovey, Masahiro Ono, Michael Flossdorf, Sabrina Bortoluzzi, Jonas Mir, Maria Colomé-Tatché, Albulena Toska, Bahire Kalfaoglu |
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| Přispěvatelé: | University of Zurich |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
Immunology Receptors Antigen T-Cell 610 Medicine & health Biology Lymphocyte Activation Immune system medicine Immunology and Allergy 10239 Institute of Laboratory Animal Science Progenitor cell Interleukin 4 Progenitor Effector T-cell receptor Cell Differentiation Cell biology Cytokine Infectious Diseases 570 Life sciences biology 590 Animals (Zoology) Cytokines Natural Killer T-Cells Il-17 Il-4 Plzf Agonist Tcr Signals Cytokine Polarization Effector Differentiation Gene Expression Dynamics Inkt Innate T Cell Development Thymus Signal transduction Biomarkers Signal Transduction |
| Zdroj: | Immunity 54, 2497-2513.e9 (2021) |
| ISSN: | 1097-4180 |
| Popis: | Summary Innate-like T cell populations expressing conserved TCRs play critical roles in immunity through diverse developmentally acquired effector functions. Focusing on the prototypical lineage of invariant natural killer T (iNKT) cells, we sought to dissect the mechanisms and timing of fate decisions and functional effector differentiation. Utilizing induced expression of the semi-invariant NKT cell TCR on double positive thymocytes, an initially highly synchronous wave of iNKT cell development was triggered by brief homogeneous TCR signaling. After reaching a uniform progenitor state characterized by IL-4 production potential and proliferation, effector subsets emerged simultaneously, but then diverged toward different fates. While NKT17 specification was quickly completed, NKT1 cells slowly differentiated and expanded. NKT2 cells resembled maturing progenitors, which gradually diminished in numbers. Thus, iNKT subset diversification occurs in dividing progenitor cells without acute TCR input but utilizes multiple active cytokine signaling pathways. These data imply a two-step model of iNKT effector differentiation. |
| Databáze: | OpenAIRE |
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