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Bortoluzzi, S.* ; Dashtsoodol, N.* ; Engleitner, T.* ; Drees, C.* ; Helmrath, S.* ; Mir, J.* ; Toska, A.* ; Flossdorf, M.* ; Öllinger, R.* ; Solovey, M. ; Colomé-Tatché, M. ; Kalfaoglu, B.* ; Ono, M.* ; Buch, T.* ; Ammon, T.* ; Rad, R.* ; Schmidt-Supprian, M.*

Brief homogeneous TCR signals instruct common iNKT progenitors whose effector diversification is characterized by subsequent cytokine signaling.

Immunity 54, 2497-2513.e9 (2021)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Il-17 ; Il-4 ; Plzf ; Agonist Tcr Signals ; Cytokine Polarization ; Effector Differentiation ; Gene Expression Dynamics ; Inkt ; Innate T Cell Development ; Thymus; Set Enrichment Analysis; Nkt Cell-development; Gamma-delta T; Zinc-finger; Innate; Expression; Plzf; Homeostasis; Il-15; Transcription
ISSN (print) / ISBN 1074-7613
e-ISSN 1097-4180
Journal Immunity
Quellenangaben Volume: 54, Issue: 11, Pages: 2497-2513.e9 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants DFG through CRC1054