Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Nat Commun. 2024 Feb 26;15(1):1752. doi: 10.1038/s41467-024-46076-3.
Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRACD142 fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRACD142 fibroblasts foster monocyte transition to CCR2CD206 macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2CD206 cells from co-cultures have a phenotype similar to intestinal CCR2CD206 macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation.
基质细胞支持上皮细胞和免疫细胞的稳态，并在炎症性肠病（IBD）发病机制中发挥重要作用。在这里，我们量化了小儿 IBD 中基质对炎症的反应，并揭示了结肠节段和肠层之间亚群特异性的炎症反应。我们使用来自鼠动态肠道损伤模型和人类离体转录组学、蛋白质和空间分析的数据，报告 PDGFRACD142 成纤维细胞和单核细胞/巨噬细胞在肠道中共同定位。在原代人成纤维细胞-单核细胞共培养物中，肠 PDGFRACD142 成纤维细胞通过粒细胞-巨噬细胞集落刺激因子（GM-CSF）促进单核细胞向 CCR2CD206 巨噬细胞的转化。来自共培养物的单核细胞衍生的 CCR2CD206 细胞具有与新诊断的小儿 IBD 患者的肠 CCR2CD206 巨噬细胞相似的表型，具有高水平的 PD-L1 和低水平的 GM-CSF 受体。该研究描述了对炎症的基质反应的亚群特异性变化，并表明肠道基质指导肠道巨噬细胞分化。
