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

Zuoan Yi; Laura L Stunz; Gail A Bishop

doi:10.1084/jem.20122135

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

Journal article

Open access

Peer reviewed

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

Zuoan Yi, Laura L Stunz and Gail A Bishop

The Journal of experimental medicine, Vol.210(6), pp.1079-1086

06/03/2013

DOI: 10.1084/jem.20122135

PMCID: PMC3674694

PMID: 23650438

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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 CD4(Cre)TRAF3(flox/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.

Cell Growth Processes - immunology

Up-Regulation

Interleukin-2 Receptor beta Subunit - metabolism

Cell Survival - genetics

T-Box Domain Proteins - immunology

Interleukin-15 - immunology

Natural Killer T-Cells - metabolism

TNF Receptor-Associated Factor 3 - genetics

Receptors, Antigen, T-Cell - immunology

Interleukin-2 Receptor beta Subunit - genetics

Receptors, Antigen, T-Cell - metabolism

Signal Transduction

Mice, Inbred C57BL

TNF Receptor-Associated Factor 3 - metabolism

Cell Survival - immunology

T-Box Domain Proteins - genetics

T-Box Domain Proteins - metabolism

Animals

Interleukin-15 - genetics

Interleukin-15 - metabolism

TNF Receptor-Associated Factor 3 - immunology

Mice

Receptors, Antigen, T-Cell - genetics

Interleukin-2 Receptor beta Subunit - immunology

Natural Killer T-Cells - immunology

Details

Title: Subtitle: TNF receptor associated factor 3 plays a key role in development and function of invariant natural killer T cells
Creators: Zuoan Yi - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Laura L Stunz
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of experimental medicine, Vol.210(6), pp.1079-1086
Publisher: United States
DOI: 10.1084/jem.20122135
PMID: 23650438
PMCID: PMC3674694
ISSN: 0022-1007
eISSN: 1540-9538
Grant note: R01 AI28847 / NIAID NIH HHS P30 ES005605 / NIEHS NIH HHS R01 AI028847 / NIAID NIH HHS
Language: English
Date published: 06/03/2013
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001207302771

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