Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells

被引：77

作者：

Yang, Baoli ^{[3
]}

Gay, Denise L. ^{[4
]}

MacLeod, Megan K. L. ^{[1
,2
,8
]}

Cao, Xiao ^{[3
]}

Hala, Tamara ^{[4
]}

Sweezer, Eileen M. ^{[3
]}

Kappler, John ^{[1
,2
,5
,6
,8
]}

Marrack, Philippa ^{[1
,2
,5
,7
,8
]}

Oliver, Paula M. ^{[1
,2
,8
]}

机构：

[1] Natl Jewish Med & Res Ctr, Integrated Dept Immunol, Denver, CO 80206 USA

[2] Univ Colorado, Hlth Sci Ctr, Denver, CO 80206 USA

[3] Univ Iowa, Carver Coll Med, Dept Obstet & Gynecol, Iowa City, IA 52242 USA

[4] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[5] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80206 USA

[6] Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80206 USA

[7] Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Denver, CO 80206 USA

[8] Natl Jewish Med & Res Ctr, Howard Hughes Med Inst, Denver, CO 80206 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 12期

关键词：

D O I：

10.1038/ni.1670

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Nedd4 and Itch are E3 ubiquitin ligases that ubiquitinate similar targets in vitro and thus are thought to function similarly. T cells lacking Itch show spontaneous activation and T helper type 2 polarization. To test whether loss of Nedd4 affects T cells in the same way, we generated Nedd4(+/+) and Nedd4(-/-) fetal liver chimeras. Nedd4(-/-) T cells developed normally but proliferated less, produced less interleukin 2 and provided inadequate help to B cells. Nedd4(-/-) T cells contained more of the E3 ubiquitin ligase Cbl-b, and Nedd4 was required for polyubiquitination of Cbl-b induced by CD28 costimulation. Our data demonstrate that Nedd4 promotes the conversion of naive T cells into activated T cells. We propose that Nedd4 and Itch ubiquitinate distinct target proteins in vivo.

引用

页码：1356 / 1363

页数：8

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