JAK/STAT-1 Signaling Is Required for Reserve Intestinal Stem Cell Activation during Intestinal Regeneration Following Acute Inflammation.
JAK/STAT-1 Signaling Is Required for Reserve Intestinal Stem Cell Activation during Intestinal Regeneration Following Acute Inflammation.
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DOI：
10.1016/j.stemcr.2017.11.015
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发表时间：
2018-01-09
影响因子：
5.9
通讯作者：
Breault DT
中科院分区：
文献类型：
--
作者：
Richmond CA;Rickner H;Shah MS;Ediger T;Deary L;Zhou F;Tovaglieri A;Carlone DL;Breault DT
肠上皮是进入外界的重要屏障，由功能不同的快速循环肠道干细胞(CBC ISCs)和缓慢循环储备ISCs(r-ISCs)维持。由于免疫系统的病理性激活可能导致上皮屏障的破坏，我们试图调查炎症对再生反应期间ISC行为的影响。在αCD3抗体诱导的小鼠小肠炎症模型中，r-ISCs被证明对损伤具有高度抵抗力，而CBCISCs则经历了凋亡。此外，r-ISCs被诱导增殖，并在功能上有助于肠道再生。进一步分析表明，炎性细胞因子干扰素-γ和肿瘤坏死因子-α导致肠样培养中r-ISC的激活，该激活可被JAK/STAT抑制剂tofacitinib阻断。这些结果强调了r-ISCs在急性肠炎症反应中的重要作用，并表明JAK/STAT-1信号是r-ISC再生反应所必需的。储备肠道干细胞(r-ISCs)在炎症后进入细胞周期，活化的r-ISCs增殖并促进肠道再生，细胞因子刺激的JAK/STAT-1信号是激活r-ISC所必需的。研究表明，在肠炎性损伤后，储备肠道干细胞(r-ISCs)处于静止状态，有助于肠道再生。相反，隐窝基底柱状间充质干细胞发生凋亡，并在即刻恢复期表现出较少的谱系贡献。炎症损伤后早期恢复期的r-ISC激活需要JAK/STAT-1信号。
The intestinal epithelium serves as an essential barrier to the outside world and is maintained by functionally distinct populations of rapidly cycling intestinal stem cells (CBC ISCs) and slowly cycling, reserve ISCs (r-ISCs). Because disruptions in the epithelial barrier can result from pathological activation of the immune system, we sought to investigate the impact of inflammation on ISC behavior during the regenerative response. In a murine model of αCD3 antibody-induced small-intestinal inflammation, r-ISCs proved highly resistant to injury, while CBC ISCs underwent apoptosis. Moreover, r-ISCs were induced to proliferate and functionally contribute to intestinal regeneration. Further analysis revealed that the inflammatory cytokines interferon gamma and tumor necrosis factor alpha led to r-ISC activation in enteroid culture, which could be blocked by the JAK/STAT inhibitor, tofacitinib. These results highlight an important role for r-ISCs in response to acute intestinal inflammation and show that JAK/STAT-1 signaling is required for the r-ISC regenerative response. Reserve intestinal stem cells (r-ISCs) enter the cell cycle following inflammation Activated r-ISCs proliferate and contribute to intestinal regeneration Cytokine-stimulated JAK/STAT-1 signaling is required for r-ISC activation Richmond et al. demonstrate that, following intestinal inflammatory injury, reserve intestinal stem cells (r-ISCs) exit quiescence and contribute to intestinal regeneration. In contrast, crypt base columnar ISCs undergo apoptosis and show a reduced lineage contribution in the immediate recovery period. JAK/STAT-1 signaling is required for r-ISC activation during the early recovery period following inflammatory injury.
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DOI：
10.4161/jkst.23820
发表时间：
2013-01-01
期刊：
JAK-STAT
影响因子：
--
作者：
Rauch I;Müller M;Decker T
通讯作者：
Decker T
DOI：
10.1073/pnas.1013004108
发表时间：
2011-01-04
影响因子：
11.1
作者：
Montgomery, Robert K.;Carlone, Diana L.;Breault, David T.
通讯作者：
Breault, David T.
DOI：
10.4049/jimmunol.1301757
发表时间：
2014-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kominsky DJ;Campbell EL;Ehrentraut SF;Wilson KE;Kelly CJ;Glover LE;Collins CB;Bayless AJ;Saeedi B;Dobrinskikh E;Bowers BE;MacManus CF;Müller W;Colgan SP;Bruder D
通讯作者：
Bruder D
影响因子：
56.9
作者：
Chin, YE;Kitagawa, M;Fu, XY
通讯作者：
Fu, XY
DOI：
10.1073/pnas.0903487106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Cheon, HyeonJoo;Stark, George R.
通讯作者：
Stark, George R.