Critical role of interferons in gastrointestinal injury repair.
Critical role of interferons in gastrointestinal injury repair.
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DOI：
10.1038/s41467-021-22928-0
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发表时间：
2021-05-11
影响因子：
16.6
通讯作者：
Kotenko SV
中科院分区：
文献类型：
--
作者：
McElrath C;Espinosa V;Lin JD;Peng J;Sridhar R;Dutta O;Tseng HC;Smirnov SV;Risman H;Sandoval MJ;Davra V;Chang YJ;Pollack BP;Birge RB;Galan M;Rivera A;Durbin JE;Kotenko SV
溃疡性结肠炎的病因学知之甚少，可能涉及粘膜免疫系统和肠道细菌之间复杂相互作用的干扰，细胞因子作为重要的交叉调节因子。在这里，我们使用IFN受体缺陷小鼠在葡聚糖硫酸钠（DSS）模型的急性肠损伤研究的贡献，I型和III型干扰素（IFN）的急性结肠炎的开始，进展和解决。我们发现，缺乏这两种类型的IFN受体的小鼠表现出增强的屏障破坏，杯状细胞的广泛损失和DSS诱导的损伤后结肠上皮细胞增殖减少。双IFN受体缺陷小鼠中受损的粘膜愈合是由双调蛋白表达减少驱动的，IFN信号可以在上皮或造血隔室中上调双调蛋白表达。总之，这些数据强调了IFN的多效性功能，并证明这些关键的抗病毒细胞因子也支持急性结肠损伤后的上皮再生。尽管溃疡性结肠炎很普遍，但研究很充分，其病理生理学特征仍然很差。在这里，作者使用小鼠结肠炎模型发现I型和III型干扰素（IFN）都有助于改善疾病，上皮或造血隔室中的IFN信号足以实现这种保护作用。
The etiology of ulcerative colitis is poorly understood and is likely to involve perturbation of the complex interactions between the mucosal immune system and the commensal bacteria of the gut, with cytokines acting as important cross-regulators. Here we use IFN receptor-deficient mice in a dextran sulfate sodium (DSS) model of acute intestinal injury to study the contributions of type I and III interferons (IFN) to the initiation, progression and resolution of acute colitis. We find that mice lacking both types of IFN receptors exhibit enhanced barrier destruction, extensive loss of goblet cells and diminished proliferation of epithelial cells in the colon following DSS-induced damage. Impaired mucosal healing in double IFN receptor-deficient mice is driven by decreased amphiregulin expression, which IFN signaling can up-regulate in either the epithelial or hematopoietic compartment. Together, these data underscore the pleiotropic functions of IFNs and demonstrate that these critical antiviral cytokines also support epithelial regeneration following acute colonic injury. Despite being prevalent yet well studied, ulcerative colitis still has poorly characterized pathophysiology. Here the authors use mouse colitis models to find that type I and III interferon (IFN) both contribute to ameliorating the disease, with IFN signaling in either the epithelial or hematopoietic compartment sufficient for this protective effect.
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影响因子：
4.6
作者：
Dubé PE;Liu CY;Girish N;Washington MK;Polk DB
通讯作者：
Polk DB
影响因子：
4.7
作者：
Budhwani M;Mazzieri R;Dolcetti R
通讯作者：
Dolcetti R
影响因子：
3.7
作者：
Chassaing B;Srinivasan G;Delgado MA;Young AN;Gewirtz AT;Vijay-Kumar M
通讯作者：
Vijay-Kumar M
DOI：
10.1073/pnas.0708469104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Abe, Kazumichi;Nguyen, Kim Phung;Raz, Eyal
通讯作者：
Raz, Eyal
影响因子：
65.1
作者：
de Souza, Heitor S. P.;Fiocchi, Claudio;Iliopoulos, Dimitrios
通讯作者：
Iliopoulos, Dimitrios