TRAF5 negatively regulates TLR signaling in B lymphocytes

Claire M Buchta; Gail A Bishop

doi:10.4049/jimmunol.1301901

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TRAF5 negatively regulates TLR signaling in B lymphocytes

Journal article

Peer reviewed

TRAF5 negatively regulates TLR signaling in B lymphocytes

Claire M Buchta and Gail A Bishop

The Journal of immunology (1950), Vol.192(1), pp.145-150

01/01/2014

DOI: 10.4049/jimmunol.1301901

PMCID: PMC3872259

PMID: 24259503

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Abstract

The cytoplasmic adaptor proteins TNFR-associated factor (TRAF)3 and TRAF6 are important mediators of TLR signaling. To our knowledge, we show in this study for the first time that another TRAF family member, TRAF5, is a negative regulator of TLR signaling. B lymphocytes from TRAF5(-/-) mice produced more IL-6, IL-12p40, IL-10, TNF-α, and IgM than did wild-type B cells after TLR stimulation. Consistent with these data, exogenous overexpression of TRAF5 in B cells inhibited TLR-mediated cytokine and Ab production. TLR stimulation of TRAF5-deficient B cells did not affect cell survival, proliferation, or NF-κB activation but resulted in markedly enhanced phosphorylation of the MAPKs ERK1/2 and JNK. TRAF5 negatively regulated TLR signaling in a cell-specific manner, because TRAF5(-/-) macrophages and dendritic cells showed less dramatic differences in TLR-mediated cytokine production than B cells. Following TLR stimulation, TRAF5 associated in a complex with the TLR adaptor protein MyD88 and the B cell-specific positive regulator of TLR signaling TAB2. Furthermore, TRAF5 negatively regulated the association of TAB2 with its signaling partner TRAF6 after TLR ligation in B cells. To our knowledge, these data provide the first evidence that TRAF5 acts as a negative regulator of TLR signaling.

Signal Transduction

Cell Line

Antibody Formation - immunology

Myeloid Differentiation Factor 88

TNF Receptor-Associated Factor 5 - metabolism

Mice, Knockout

Macrophages - metabolism

TNF Receptor-Associated Factor 5 - genetics

Animals

B-Lymphocytes - immunology

Protein Binding

Mice

Toll-Like Receptors - metabolism

B-Lymphocytes - metabolism

Cytokines - biosynthesis

Dendritic Cells - metabolism

Details

Title: Subtitle: TRAF5 negatively regulates TLR signaling in B lymphocytes
Creators: Claire M Buchta - Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.192(1), pp.145-150
DOI: 10.4049/jimmunol.1301901
PMID: 24259503
PMCID: PMC3872259
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: P30 ES005605 / NIEHS NIH HHS R01 AI028847 / NIAID NIH HHS I01 BX001702 / BLRD VA P30 CA086862 / NCI NIH HHS
Language: English
Date published: 01/01/2014
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001203502771

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