Journal article
Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation
Immunity, Vol.25(6), pp.929-940
12/01/2006
DOI: 10.1016/j.immuni.2006.10.012
PMID: 02955961
Abstract
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−/− T 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.
Details
- Title: Subtitle
- Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation
- Creators
- Paula M. OliverXiao CaoGeorge Scott WorthenPeijun ShiNatalie BrionesMegan MacLeodJanice WhitePatricia KirbyJohn KapplerPhilippa MarrackBaoli Yang - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Immunity, Vol.25(6), pp.929-940
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.immuni.2006.10.012
- PMID
- 02955961
- ISSN
- 1074-7613
- Language
- English
- Date published
- 12/01/2006
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9983557775602771
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