TRAF5 negatively regulates TLR signaling in B lymphocytes.
J Immunol
; 192(1): 145-50, 2014 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-24259503
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Transdução de Sinais
/
Fator 5 Associado a Receptor de TNF
/
Receptores Toll-Like
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2014
Tipo de documento:
Article