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The Journal of Experimental Medicine
Article
License: CC BY NC SA
Data sources: UnpayWall
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PubMed Central
Other literature type . 2013
Data sources: PubMed Central
The Journal of Experimental Medicine
Article . 2013 . Peer-reviewed
Data sources: Crossref
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TNF receptor associated factor 3 plays a key role in development and function of invariant natural killer T cells

Authors: Yi, Zuoan; Stunz, Laura L.; Bishop, Gail A.;

TNF receptor associated factor 3 plays a key role in development and function of invariant natural killer T cells

Abstract

TCR signaling is a prerequisite for early stage development of invariant natural killer T (iNKT) cells, whereas IL-15 signaling is required for expansion and maturation at later stages. In this study, we show that TNF receptor associated factor 3 (TRAF3) plays a critical role in the transition between these two distinct signaling pathways and developmental stages. TRAF3-deficient iNKT cells in CD4CreTRAF3flox/flox (T-TRAF3−/−) mice exhibit defective up-regulation of T-bet and CD122, two critical molecules for IL-15 signaling, and as a consequence, IL-15–mediated iNKT cell proliferation and survival are impaired. Consistently, development of iNKT cells in T-TRAF3−/− mice shows a major defect at developmental stages 2 and 3, but not stages 0 and 1. We further demonstrated that defective T-bet up-regulation occurring during the stage 1 to stage 2 transition results from reduced TCR signaling in TRAF3−/− iNKT cells. In addition, mature TRAF3−/− iNKT cells displayed defective cytokine responses upon TCR stimulation. Collectively, our results reveal that by modulating the relative strength of TCR signaling, TRAF3 is an important regulator of iNKT cell development and functions.

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Keywords

Interleukin-15, TNF Receptor-Associated Factor 3, Cell Survival, Brief Definitive Report, Receptors, Antigen, T-Cell, Cell Growth Processes, Up-Regulation, Interleukin-2 Receptor beta Subunit, Mice, Inbred C57BL, Mice, Animals, Natural Killer T-Cells, T-bet Transcription Factor, T-Box Domain Proteins, Signal Transduction

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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    31
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
31
Top 10%
Top 10%
Top 10%
Green
hybrid