Protein Kinase C-θ Mediates Negative Feedback on Regulatory T Cell Function

被引：235

作者：

Zanin-Zhorov, Alexandra ^{[1
]}

Ding, Yi ^{[1
]}

Kumari, Sudha ^{[1
]}

Attur, Mukundan ^{[2
,3
]}

Hippen, Keli L. ^{[4
,5
]}

Brown, Maryanne ^{[6
]}

Blazar, Bruce R. ^{[4
,5
]}

Abramson, Steven B. ^{[2
,3
]}

Lafaille, Juan J. ^{[1
]}

Dustin, Michael L. ^{[1
]}

机构：

[1] NYU, Sch Med, Mol Pathogenesis Program,Dept Pathol, Helen & Martin Kimmel Ctr Biol & Med,Skirball Ins, New York, NY 10016 USA

[2] NYU, Sch Med, Div Rheumatol, New York, NY 10003 USA

[3] NYU, Hosp Joint Dis, New York, NY 10003 USA

[4] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA

[5] Univ Minnesota, Dept Pediat, Div Bone Blood & Marrow Transplantat, Minneapolis, MN 55455 USA

[6] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA

来源：

SCIENCE | 2010年 / 328卷 / 5976期

关键词：

PKC-THETA; KAPPA-B; ACTIVATION; MECHANISMS; THERAPY; POTENT; FOXP3; BETA;

D O I：

10.1126/science.1186068

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

T cell receptor (TCR)-dependent regulatory T cell (T-reg) activity controls effector T cell (T-eff) function and is inhibited by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Protein kinase C-theta (PKC-theta) recruitment to the immunological synapse is required for full T-eff activation. In contrast, PKC-theta was sequestered away from the T-reg immunological synapse. Furthermore, PKC-theta blockade enhanced T-reg function, demonstrating PKC-theta inhibits T-reg-mediated suppression. Inhibition of PKC-theta protected T-reg from inactivation by TNF-alpha, restored activity of defective T-reg from rheumatoid arthritis patients, and enhanced protection of mice from inflammatory colitis. T-reg freed of PKC-theta-mediated inhibition can function in the presence of inflammatory cytokines and thus have therapeutic potential in control of inflammatory diseases.

引用

页码：372 / 376

页数：5

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