Neutrophils Promote Amphiregulin Production in Intestinal Epithelial Cells through TGF-β and Contribute to Intestinal Homeostasis.
Neutrophils Promote Amphiregulin Production in Intestinal Epithelial Cells through TGF-β and Contribute to Intestinal Homeostasis.
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DOI：
10.4049/jimmunol.1800003
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发表时间：
2018-10-15
期刊：
影响因子：
--
通讯作者：
Cong Y
中科院分区：
文献类型：
--
作者：
Chen F;Yang W;Huang X;Cao AT;Bilotta AJ;Xiao Y;Sun M;Chen L;Ma C;Liu X;Liu CG;Yao S;Dann SM;Liu Z;Cong Y
当肠上皮屏障被破坏和肠道微生物群侵入时，中性粒细胞是炎症部位的第一反应者。尽管目前的努力在理解的作用，中性粒细胞在肠道内稳态，中性粒细胞和肠上皮细胞（IEC）之间的复杂的相互作用仍然没有得到很好的表征。在这里，我们证明，中性粒细胞增强双调蛋白（AREG），EGFR配体家族的成员，由IEC，促进IEC屏障功能和组织修复的生产。由于葡聚糖硫酸钠（DSS）损伤后IEC产生的AREG减少，嗜中性粒细胞的消耗导致小鼠中更严重的结肠炎。AREG的施用恢复了上皮屏障功能并改善了结肠炎。此外，中性粒细胞来源的TGFβ促进IEC产生AREG。在机制上，TGFβ激活MEK 1/2信号传导，并且抑制MEK 1/2消除了IEC产生TGFβ诱导的AREG。总的来说，这些研究结果表明，中性粒细胞在维持IEC屏障功能和稳态中起着重要作用。
Neutrophils are the first responders to sites of inflammation when the intestinal epithelial barrier is breached and the gut microbiota invade. Despite current efforts in understanding the role of neutrophils in intestinal homeostasis, the complex interactions between neutrophils and intestinal epithelial cells (IECs) is still not well characterized. Here, we demonstrate that neutrophils enhanced production of amphiregulin (AREG), a member of EGFR ligand family, by IECs, which promoted IEC barrier function and tissue repair. Depletion of neutrophils resulted in more severe colitis in mice due to decreased AREG production by IECs upon dextran sodium sulfate (DSS) insult. Administration of AREG restored epithelial barrier function and ameliorated colitis. Furthermore, neutrophil derived TGFβ promoted AREG production by IECs. Mechanistically, TGFβ activated MEK1/2 signaling, and inhibition of MEK1/2 abrogated TGFβ-induced AREG production by IECs. Collectively, these findings reveal that neutrophils play an important role in the maintenance of IEC barrier function and homeostasis.
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影响因子：
3.9
作者：
Moustakas A;Heldin CH
通讯作者：
Heldin CH
影响因子：
32.4
作者：
Campbell EL;Bruyninckx WJ;Kelly CJ;Glover LE;McNamee EN;Bowers BE;Bayless AJ;Scully M;Saeedi BJ;Golden-Mason L;Ehrentraut SF;Curtis VF;Burgess A;Garvey JF;Sorensen A;Nemenoff R;Jedlicka P;Taylor CT;Kominsky DJ;Colgan SP
通讯作者：
Colgan SP
影响因子：
2.4
作者：
Bischoff SC;Barbara G;Buurman W;Ockhuizen T;Schulzke JD;Serino M;Tilg H;Watson A;Wells JM
通讯作者：
Wells JM
DOI：
10.4049/jimmunol.1501541
发表时间：
2016-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chen F;Cao A;Yao S;Evans-Marin HL;Liu H;Wu W;Carlsen ED;Dann SM;Soong L;Sun J;Zhao Q;Cong Y
通讯作者：
Cong Y
影响因子：
64.5
作者：
Kaiko GE;Ryu SH;Koues OI;Collins PL;Solnica-Krezel L;Pearce EJ;Pearce EL;Oltz EM;Stappenbeck TS
通讯作者：
Stappenbeck TS