TRAF1 is a negative regulator of TNF signaling. enhanced TNF signaling in TRAF1-deficient mice. |
| |
| Authors: | E N Tsitsikov D Laouini I F Dunn T Y Sannikova L Davidson F W Alt R S Geha |
| |
| Affiliation: | Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. tsitsikov_e@hub.tch.harvard.edu |
| |
| Abstract: | 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-kappa B 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. |
| |
| Keywords: | |
|
|
