The Kinase PKCα Selectively Upregulates Interleukin-17A during Th17 Cell Immune Responses

被引：36

作者：

Meisel, Marlies ^{[1
]}

Hermann-Kleiter, Natascha ^{[1
]}

Hinterleitner, Reinhard ^{[1
]}

Gruber, Thomas ^{[1
]}

Wachowicz, Katarzyna ^{[1
]}

Pfeifhofer-Obermair, Christa ^{[1
]}

Fresser, Friedrich ^{[1
]}

Leitges, Michael ^{[2
]}

Soldani, Cristiana ^{[3
,4
]}

Viola, Antonella ^{[3
,4
]}

Kaminski, Sandra ^{[1
]}

Baier, Gottfried ^{[1
]}

机构：

[1] Med Univ Innsbruck, Div Translat Cell Genet, Dept Pharmacol & Genet, A-6020 Innsbruck, Austria

[2] Biotechnol Ctr Oslo, N-0317 Oslo, Norway

[3] Univ Milan, Inst Clin Humanitas, IRCCS, I-20089 Milan, Italy

[4] Univ Milan, Dept Translat Med, I-20089 Milan, Italy

来源：

IMMUNITY | 2013年 / 38卷 / 01期

基金：

奥地利科学基金会;

关键词：

GROWTH-FACTOR-BETA; TGF-BETA; T-CELLS; MULTIPLE-SCLEROSIS; IN-VIVO; DIFFERENTIATION; CYTOKINE; IL-17; SUPPRESSION; PLASTICITY;

D O I：

10.1016/j.immuni.2012.09.021

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Transforming growth-factor beta (TGF beta) has been implicated in T helper 17 (Th17) cell biology and in triggering expression of interleukin-17A (IL-17A), which is a key Th17 cell cytokine. Deregulated TGF beta receptor (TGF beta R) signaling has been implicated in Th17-cell-mediated autoimmune pathogenesis. Nevertheless, the full molecular mechanisms involved in the activation of the TGF beta R pathway in driving IL-17A expression remain unknown. Here, we identified protein kinase C alpha (PKC alpha) as a signaling intermediate specific to the Th17 cell subset in the activation of TGF beta RI. We have shown that PKCa physically interacts and functionally cooperates with TGF beta RI to promote robust SMAD2-3 activation. Furthermore, PKC alpha-deficient (Prkca(-/-)) cells demonstrated a defect in SMAD-dependent IL-2 suppression, as well as decreased STAT3 DNA binding within the II17a promoter. Consistently, Prkca(-/-) cells failed to mount appropriate IL-17A, but not IL-17F, responses in vitro and were resistant to induction of Th17-cell-dependent experimental autoimmune encephalomyelitis in vivo.

引用

页码：41 / 52

页数：12

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