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

共 46 条

[1] Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: Implications for parasite persistence [J].

Babu, S ;

Blauvelt, CP ;

Kumaraswami, V ;

Nutman, TB .

JOURNAL OF IMMUNOLOGY, 2006, 176 (05) :3248-3256

[2] E3 ubiquitin ligases and their control of T cell autoreactivity [J].

Bonnevier, JL ;

Zhang, R ;

Mueller, DL .

ARTHRITIS RESEARCH & THERAPY, 2005, 7 (06) :233-242

[3] Cutting edge: T cell requirement for CD28 costimulation is due to negative regulation of TCR signals by PTEN [J].

Buckler, Jodi L. ;

Walsh, Patrick T. ;

Porrett, Paige M. ;

Choi, Yongwon ;

Turka, Laurence A. .

JOURNAL OF IMMUNOLOGY, 2006, 177 (07) :4262-4266

[4]

CAO XR, 2001, SCI SIGNAL IN PRESS

[5] Cbl-b regulates the CD28 dependence of T-cell activation [J].

Chiang, YPJ ;

Kole, HK ;

Brown, K ;

Naramura, M ;

Fukuhara, S ;

Hu, RJ ;

Jang, IK ;

Gutkind, JS ;

Shevach, E ;

Gu, H .

NATURE, 2000, 403 (6766) :216-220

[6] ATP-DEPENDENT CONJUGATION OF RETICULOCYTE PROTEINS WITH THE POLYPEPTIDE REQUIRED FOR PROTEIN-DEGRADATION [J].

CIECHANOVER, A ;

HELLER, H ;

ELIAS, S ;

HAAS, AL ;

HERSHKO, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (03) :1365-1368

[7] Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting [J].

Ciechanover, A .

CELL DEATH AND DIFFERENTIATION, 2005, 12 (09) :1178-1190

[8] Impaired Fas response and autoimmunity in Pten+/- mice [J].

Di Cristofano, A ;

Kotsi, P ;

Peng, YF ;

Cordon-Cardo, C ;

Elkon, KB ;

Pandolfi, PP .

SCIENCE, 1999, 285 (5436) :2122-2125

[9]

DONOVAN JA, 1994, J BIOL CHEM, V269, P22921

[10] Dysregulation of T lymphocyte function in itchy mice:: a role for itch in TH2 differentiation [J].

Fang, DY ;

Elly, C ;

Gao, BX ;

Fang, N ;

Altman, Y ;

Joazeiro, C ;

Hunter, T ;

Copeland, N ;

Jenkins, N ;

Liu, YC .

NATURE IMMUNOLOGY, 2002, 3 (03) :281-287

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