期刊
IMMUNITY
卷 25, 期 6, 页码 929-940出版社
CELL PRESS
DOI: 10.1016/j.immuni.2006.10.012
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资金
- NHLBI NIH HHS [R01 HL105834] Funding Source: Medline
- NIAID NIH HHS [AI-22295, R01 AI052225, P01 AI022295, AI-52225] Funding Source: Medline
- NIDDK NIH HHS [P50 DK052617-100007, P50 DK52617, P50 DK052617] Funding Source: Medline
Nedd4 family interacting protein-1 (Ndfip1) is a protein whose only known function is that it binds Nedd4, a HECT-type E3 ubiquitin ligase. Here we show that mice lacking Ndfip1 developed severe inflammation of the skin and lung and died prematurely. This condition was due to a defect in Ndfip1(-/-) T cells. Ndfip1(-/-) cells were activated, and they proliferated and adopted a T helper 2 (Th2) phenotype more readily than did their Ndfip1(+/+) counterparts. This phenotype resembled that of Itchy mutant mice, suggesting that Ndfip1 might affect the function of Itch, an E3 ubiquitin ligase. We show that T cell activation promoted both Ndfip1 expression and its association with Itch. In the absence of Ndfip1, JunB half-life was prolonged after T cell activation. Thus, in the absence of Ndfip1, Itch is inactive and JunB accumulates. As a result, T cells produce Th2 cytokines and promote Th2-mediated inflammatory disease.
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