TRAF1 is a negative regulator of TNF signaling: Enhanced TNF signaling in TRAF1-deficient mice

被引：156

作者：

Tsitsikov, EN ^{[1
]}

Laouini, D

Dunn, IF

Sannikova, TY

Davidson, L

Alt, FW

Geha, RS

机构：

[1] Harvard Univ, Sch Med, Div Immunol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

来源：

IMMUNITY | 2001年 / 15卷 / 04期

关键词：

D O I：

10.1016/S1074-7613(01)00207-2

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

TNF receptor-associated factor 1 (TRAF1) is a unique TRAF protein because it lacks a RING finger domain and is predominantly expressed in activated lymphocytes. To elucidate the function of TRAF1, we generated TRAF1-deficient mice. TRAF1(-/-) mice are viable and have normal lymphocyte development. TRAF1(-/-) T cells exhibit stronger than wild-type (WT) T cell proliferation to anti-CD3 mAb, which persisted in the presence of IL-2 or anti-CD28 antibodies. Activated TRAF1(-/-) T cells, but not TRAF1(+/+) T cells, responded to TNF by proliferation and activation of the NF-kappaB and AP-1 signaling pathways. This TNF effect was mediated by TNFR2 (p75) but not by TNFR1 (p55). Furthermore, skin from TRAF1(-/-) mice was hypersensitive to TNF-induced necrosis. These findings suggest that TRAF1 is a negative regulator of TNF signaling.

引用

页码：647 / 657

页数：11

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