STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.
STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.
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DOI：
10.1084/jem.20082683
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发表时间：
2009-07-06
期刊：
影响因子：
--
通讯作者：
Becker C
中科院分区：
文献类型：
--
作者：
Pickert G;Neufert C;Leppkes M;Zheng Y;Wittkopf N;Warntjen M;Lehr HA;Hirth S;Weigmann B;Wirtz S;Ouyang W;Neurath MF;Becker C
信号转导及转录激活因子（STAT）3是一种多效性转录因子，在多种组织的细胞因子信号传导中具有重要功能。然而，STAT3在肠上皮中的作用尚未被充分了解。我们证明结肠炎症的发展与肠上皮细胞（IECs）中STAT3活性的诱导有关。对基因工程小鼠的研究表明，葡聚糖硫酸钠结肠炎中上皮STAT3的激活依赖于白细胞介素（IL）-22而非IL - 6。IL - 22是由结肠CD11c +细胞在Toll样受体刺激下分泌的。肠上皮细胞特异性缺失STAT3活性的条件性敲除小鼠对实验性结肠炎高度易感，这表明上皮STAT3调节肠道内稳态。在诱导结肠炎后，STAT3IEC - KO小鼠表现出上皮修复的显著缺陷。基因芯片分析表明，STAT3调节细胞应激反应、细胞凋亡以及与肠上皮细胞伤口愈合相关的通路。一致地，在体内伤口愈合实验中发现IL - 22和上皮STAT3都很重要。总之，我们的数据表明肠上皮STAT3的激活通过促进依赖于IL - 22的黏膜伤口愈合来调节肠道的免疫内稳态。
Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c+ cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific deletion of STAT3 activity were highly susceptible to experimental colitis, indicating that epithelial STAT3 regulates gut homeostasis. STAT3IEC-KO mice, upon induction of colitis, showed a striking defect of epithelial restitution. Gene chip analysis indicated that STAT3 regulates the cellular stress response, apoptosis, and pathways associated with wound healing in IECs. Consistently, both IL-22 and epithelial STAT3 were found to be important in wound-healing experiments in vivo. In summary, our data suggest that intestinal epithelial STAT3 activation regulates immune homeostasis in the gut by promoting IL-22–dependent mucosal wound healing.
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影响因子：
64.8
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
通讯作者：
Colonna, Marco
影响因子：
15.9
作者：
Sugimoto, Ken;Ogawa, Atsuhiro;Mizoguchi, Atsushi
通讯作者：
Mizoguchi, Atsushi
影响因子：
32.4
作者：
Takeda, K;Clausen, BE;Akira, S
通讯作者：
Akira, S
DOI：
10.1073/pnas.0405979102
发表时间：
2005-01-04
影响因子：
11.1
作者：
Pull, SL;Doherty, JM;Stappenbeck, TS
通讯作者：
Stappenbeck, TS
影响因子：
50.3
作者：
Bollrath, Julia;Phesse, Toby J.;Greten, Florian R.
通讯作者：
Greten, Florian R.