期刊
NATURE IMMUNOLOGY
卷 9, 期 12, 页码 1356-1363出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1670
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- NIAID NIH HHS [R37 AI018785, P01 AI022295, R37 AI018785-20, R01 AI093566, P01 AI022295-24] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R37AI018785, P01AI022295, R01AI093566] Funding Source: NIH RePORTER
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.
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