School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, China.
Department of Stomatology, Chifeng Maternity Hospital, Chifeng, Inner Mongolia, China.
J Transl Med. 2024 Oct 6;22(1):905. doi: 10.1186/s12967-024-05673-y.
The incidence of inflammatory bowel disease (IBD) is on the rise in developing countries, and investigating the underlying mechanisms of IBD is essential for the development of targeted therapeutic interventions. Interferon regulatory factor 7 (IRF7) is known to exert pro-inflammatory effects in various autoimmune diseases, yet its precise role in the development of colitis remains unclear.
We analyzed the clinical significance of IRF7 in ulcerative colitis (UC) by searching RNA-Seq databases and collecting tissue samples from clinical UC patients. And, we performed dextran sodium sulfate (DSS)-induced colitis modeling using WT and Irf7 mice to explore the mechanism of IRF7 action on colitis.
In this study, we found that IRF7 expression is significantly reduced in patients with UC, and also demonstrated that Irf7 mice display heightened susceptibility to DSS-induced colitis, accompanied by elevated levels of colonic and serum pro-inflammatory cytokines, suggesting that IRF7 is able to inhibit colitis. This increased susceptibility is linked to compromised intestinal barrier integrity and impaired expression of key molecules, including Muc2, E-cadherin, β-catenin, Occludin, and Interleukin-28A (IL-28A), a member of type III interferon (IFN-III), but independent of the deficiency of classic type I interferon (IFN-I) and type II interferon (IFN-II). The stimulation of intestinal epithelial cells by recombinant IL-28A augments the expression of Muc2, E-cadherin, β-catenin, and Occludin. The recombinant IL-28A protein in mice counteracts the heightened susceptibility of Irf7 mice to colitis induced by DSS, while also elevating the expression of Muc2, E-cadherin, β-catenin, and Occludin, thereby promoting the integrity of the intestinal barrier.
These findings underscore the pivotal role of IRF7 in preserving intestinal homeostasis and forestalling the onset of colitis.
炎症性肠病（IBD）在发展中国家的发病率呈上升趋势，因此研究 IBD 的潜在机制对于开发靶向治疗干预措施至关重要。干扰素调节因子 7（IRF7）已知在各种自身免疫性疾病中发挥促炎作用，但它在结肠炎发展中的确切作用尚不清楚。
我们通过搜索 RNA-Seq 数据库并收集临床 UC 患者的组织样本，分析了 IRF7 在溃疡性结肠炎（UC）中的临床意义。并且，我们使用 WT 和 Irf7 小鼠进行葡聚糖硫酸钠（DSS）诱导的结肠炎模型，以探讨 IRF7 作用于结肠炎的机制。
在这项研究中，我们发现 IRF7 的表达在 UC 患者中显著降低，并且还表明 Irf7 小鼠对 DSS 诱导的结肠炎表现出更高的易感性，伴随着结肠和血清中促炎细胞因子水平的升高，表明 IRF7 能够抑制结肠炎。这种易感性的增加与肠道屏障完整性受损和关键分子（包括 Muc2、E-钙粘蛋白、β-连环蛋白、Occludin 和白细胞介素 28A（IL-28A），一种 III 型干扰素（IFN-III）的成员）表达受损有关，但与经典 I 型干扰素（IFN-I）和 II 型干扰素（IFN-II）的缺乏无关。重组 IL-28A 刺激肠上皮细胞可增强 Muc2、E-钙粘蛋白、β-连环蛋白和 Occludin 的表达。重组 IL-28A 蛋白在小鼠中可抵抗 DSS 诱导的 Irf7 小鼠对结肠炎的易感性，同时还可提高 Muc2、E-钙粘蛋白、β-连环蛋白和 Occludin 的表达，从而促进肠道屏障的完整性。
这些发现强调了 IRF7 在维持肠道内稳态和预防结肠炎发生中的关键作用。
