Dimitrov Georges, Ryffel Bernhard, Togbe Dieudonnée, Quesniaux Valérie
Pediatrics and pediatric surgery, University Hospital Center of Orleans, Orleans 45100, France; Laboratory of Immuno-Neuro Modulation (INEM), UMR7355, CNRS and University of Orleans, 45071, Orleans, France.
Laboratory of Immuno-Neuro Modulation (INEM), UMR7355, CNRS and University of Orleans, 45071, Orleans, France.
Trends Mol Med. 2025 Feb;31(2):165-180. doi: 10.1016/j.molmed.2024.10.002. Epub 2024 Oct 23.
Inflammatory bowel diseases (IBD) are chronic, incurable pathologies with unknown causes, affecting millions of people. Pediatric-onset IBD, starting before the age of 18 years, are increasing, with more aggressive and extensive features than adult-onset IBD. These differences remain largely unexplained. Intestinal mucosal damage, cell death, DNA release from nuclear, mitochondrial, or microbiota sources, and DNA-sensing activating the cGAS-STING pathway may contribute to disease evolution. Increased colonic cGAS and STING are increasingly reported in experimental and human IBD. However, limited knowledge of the mechanisms involved hinders the development of new therapeutic options. Here, we discuss recent advances and unresolved questions regarding DNA release, DNA sensor activation, and the role and therapeutic potential of the cGAS-STING pathway in inflammatory colitis.
炎症性肠病（IBD）是病因不明的慢性、不治之症，影响着数百万人。18岁之前发病的儿童期IBD正在增加，其特征比成人期IBD更具侵袭性和广泛性。这些差异在很大程度上仍无法解释。肠道黏膜损伤、细胞死亡、来自细胞核、线粒体或微生物群来源的DNA释放，以及激活cGAS-STING途径的DNA传感可能促进疾病进展。在实验性和人类IBD中，越来越多的报道称结肠中cGAS和STING增加。然而，对相关机制的了解有限阻碍了新治疗方案的开发。在这里，我们讨论了关于DNA释放、DNA传感器激活以及cGAS-STING途径在炎症性结肠炎中的作用和治疗潜力的最新进展和未解决的问题。
