| First Author | Buchta CM | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 1 | Pages | 145-50 |
| PubMed ID | 24259503 | Mgi Jnum | J:207102 |
| Mgi Id | MGI:5554467 | Doi | 10.4049/jimmunol.1301901 |
| Citation | Buchta CM, et al. (2014) TRAF5 negatively regulates TLR signaling in B lymphocytes. J Immunol 192(1):145-50 |
| abstractText | 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-alpha, 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-kappaB 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. |
