The adaptor TRAF3 restrains the lineage determination of thymic regulatory T cells by modulating signaling via the receptor for IL-2

Zuoan Yi; Wai Wai Lin; Laura L Stunz; Gail A Bishop

doi:10.1038/ni.2944

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The adaptor TRAF3 restrains the lineage determination of thymic regulatory T cells by modulating signaling via the receptor for IL-2

Journal article

Peer reviewed

The adaptor TRAF3 restrains the lineage determination of thymic regulatory T cells by modulating signaling via the receptor for IL-2

Zuoan Yi, Wai Wai Lin, Laura L Stunz and Gail A Bishop

Nature immunology, Vol.15(9), pp.866-874

09/2014

DOI: 10.1038/ni.2944

PMCID: PMC4139452

PMID: 25029551

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Abstract

The number of Foxp3+ regulatory T cells (Treg cells) must be tightly controlled for efficient suppression of autoimmunity with no impairment of normal immune responses. Here we found that the adaptor TRAF3 was intrinsically required for restraining the lineage determination of thymic Treg cells. T cell-specific deficiency in TRAF3 resulted in a two- to threefold greater frequency of Treg cells, due to the more efficient transition of precursors of Treg cells into Foxp3+ Treg cells. TRAF3 dampened interleukin 2 (IL-2) signaling by facilitating recruitment of the tyrosine phosphatase TCPTP to the IL-2 receptor complex, which resulted in dephosphorylation of the signaling molecules Jak1 and Jak3 and negative regulation of signaling via Jak and the transcription factor STAT5. Our results identify a role for TRAF3 as an important negative regulator of signaling via the IL-2 receptor that affects the development of Treg cells.

Forkhead Transcription Factors - immunology

Janus Kinase 3 - immunology

Protein Tyrosine Phosphatase, Non-Receptor Type 2 - immunology

STAT5 Transcription Factor - immunology

Thymus Gland - cytology

Janus Kinase 1 - immunology

T-Lymphocytes, Regulatory - immunology

Cell Differentiation - immunology

Signal Transduction - immunology

Animals

Interleukin-2 - immunology

Autoimmunity - immunology

TNF Receptor-Associated Factor 3 - immunology

Mice

Details

Title: Subtitle: The adaptor TRAF3 restrains the lineage determination of thymic regulatory T cells by modulating signaling via the receptor for IL-2
Creators: Zuoan Yi - Department of Microbiology, University of Iowa, Iowa, USA
Wai Wai Lin - 1] Department of Microbiology, University of Iowa, Iowa, USA. Graduate Immunology Program, University of Iowa, Iowa, USA
Laura L Stunz - Department of Microbiology, University of Iowa, Iowa, USA
Gail A Bishop - 1] Department of Microbiology, University of Iowa, Iowa, USA. Graduate Immunology Program, University of Iowa, Iowa, USA. Department of Internal Medicine, University of Iowa, Iowa, USA. Veterans Affairs Medical Center, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Nature immunology, Vol.15(9), pp.866-874
DOI: 10.1038/ni.2944
PMID: 25029551
PMCID: PMC4139452
NLM abbreviation: Nat Immunol
ISSN: 1529-2908
eISSN: 1529-2916
Publisher: United States
Grant note: P30 ES005605 / NIEHS NIH HHS AI28847 / NIAID NIH HHS R01 AI028847 / NIAID NIH HHS I01 BX001702 / BLRD VA P30CA086862 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R56 AI028847 / NIAID NIH HHS 5T32AI007260-27 / NIAID NIH HHS
Language: English
Date published: 09/2014
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001150902771

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