Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
Curr Top Microbiol Immunol. 2014;380:19-38. doi: 10.1007/978-3-662-43492-5_2.
Twenty years ago, the observation that mice genetically deficient in IL-10 spontaneously developed severe intestinal inflammation, revealed an essential role for IL-10 in the maintenance of intestinal homeostasis. In the intervening period much has been learned about the cellular and molecular factors that are involved in IL-10-mediated regulatory pathways. Elegant experiments with conditional cell-type specific knockout strains have illustrated that IL-10 acts on both myeloid cells and T cells within the intestine to suppress innate and adaptive inflammatory responses and enhance regulatory circuits. Although several distinct cellular sources of IL-10 have been identified in the gut, CD4(+) T cells are a crucial non-redundant source of IL-10 for the regulation of intestinal inflammation. Induction of IL-10 may represent an important means through which intestinal microbiota establishes mutually beneficial commensalism with mammalian hosts, but can be exploited by certain pathogens to facilitate infection. Recent genetic studies in humans have confirmed the essential role of IL-10 in preventing deleterious inflammation in the gut. A better understanding of the molecular pathways involved in IL-10 induction and function in the intestine may facilitate the development of novel therapies for inflammatory bowel disease (IBD).
二十年前，人们观察到缺乏 IL-10 基因的小鼠会自发地出现严重的肠道炎症，这揭示了 IL-10 在维持肠道内稳态中的重要作用。在这期间，人们已经了解了许多涉及 IL-10 介导的调节途径的细胞和分子因素。利用条件性细胞类型特异性敲除株的巧妙实验表明，IL-10 在内脏的髓系细胞和 T 细胞上发挥作用，以抑制先天和适应性炎症反应，并增强调节回路。尽管在肠道中已经鉴定出几种不同的 IL-10 细胞来源，但 CD4(+) T 细胞是调节肠道炎症的 IL-10 的关键非冗余来源。IL-10 的诱导可能代表了肠道微生物群与哺乳动物宿主建立互利共生关系的重要手段，但某些病原体可以利用它来促进感染。最近在人类中的遗传研究证实了 IL-10 在预防肠道中有害炎症中的重要作用。更好地了解 IL-10 在肠道中的诱导和功能的分子途径可能有助于开发治疗炎症性肠病（IBD）的新疗法。
