Nakazawa Meg, Nagao Itsuma, Ambrosini Yoko M
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
BMC Mol Cell Biol. 2025 Apr 8;26(1):11. doi: 10.1186/s12860-025-00536-w.
The interplay between intestinal epithelial cells (IECs), the immune system, and the gut microbiome is pivotal for maintaining gastrointestinal homeostasis and mediating responses to ingested antigens. IECs, capable of expressing Major Histocompatibility Complex (MHC) class II molecules, are essential in modulating immune responses, especially CD4 + T cells, in both physiological and pathological contexts. The expression of MHC class II on IECs, regulated by the class II transactivator (CIITA) and inducible by cytokine IFN-γ, has been traditionally associated with professional antigen-presenting cells but is now recognized in the context of inflammatory conditions such as inflammatory bowel disease (IBD). In veterinary medicine, particularly among canine populations, MHC (or Dog Leukocyte Antigen, DLA) expression on IECs underlines its significance in intestinal immune pathologies, yet remains underexplored. This study aims to leverage canine intestinal organoids as a novel in vitro model to elucidate MHC class II expression dynamics and their implications in immune-mediated gastrointestinal diseases, bridging the gap between basic research and clinical application in canine health.
Canine colonoids derived from healthy dogs showed significant expression of MHC class II and its promoter gene, CIITA, after IFN-γ treatment. This MHC class II induction was even more pronounced in differentiated colonoids cultured in Wnt-3a-depleted medium.
This study provides insights into the role of IECs as antigen-presenting cells and demonstrates the use of intestinal organoids for investigating epithelial immune responses in inflammatory conditions.
肠道上皮细胞（IECs）、免疫系统和肠道微生物群之间的相互作用对于维持胃肠道稳态以及介导对摄入抗原的反应至关重要。能够表达主要组织相容性复合体（MHC）II类分子的IECs在生理和病理情况下调节免疫反应，尤其是CD4 + T细胞方面至关重要。IECs上MHC II类分子的表达受II类反式激活因子（CIITA）调控，并可被细胞因子IFN-γ诱导，传统上与专业抗原呈递细胞相关，但现在在炎症性肠病（IBD）等炎症性疾病的背景下也得到了认可。在兽医学中，特别是在犬类群体中，IECs上MHC（或犬白细胞抗原，DLA）的表达突出了其在肠道免疫病理学中的重要性，但仍未得到充分研究。本研究旨在利用犬肠道类器官作为一种新型体外模型，以阐明MHC II类分子的表达动态及其在免疫介导的胃肠道疾病中的意义，弥合犬类健康基础研究与临床应用之间的差距。
来自健康犬的犬结肠类器官在IFN-γ处理后显示出MHC II类分子及其启动子基因CIITA的显著表达。在缺乏Wnt-3a的培养基中培养的分化结肠类器官中，这种MHC II类分子的诱导更为明显。
本研究深入了解了IECs作为抗原呈递细胞的作用，并证明了肠道类器官在研究炎症条件下上皮免疫反应中的应用。
