How the human intestinal immune system is distinctly organized to respond to inflammation is still poorly understood. Here, we used single-cell RNA-sequencing to examine lamina propria CD45+ hematopoietic cells from patients with inflammatory bowel disease that have undergone ileal pouch-anal anastomosis, or the colon mucosa of ulcerative colitis patients. We identified a population of IL1B+ antimicrobial macrophages and FOXP3+/BATF+ T cells that are associated and expanded in inflamed tissues, which we further validated in other scRNA-seq datasets from IBD patients. CD8+ T cells were unexpectedly more abundant in the pouch than colon. Cell type specific markers obtained from single-cell RNA-sequencing was used to infer representation from bulk RNA sequencing datasets, which further implicated antimicrobial macrophages expressing IL1B with S100A8/A9 calprotectin as being associated with inflammation, as well as Bacteroides and Escherichia bacterial species. Finally, we find that non-responsiveness to anti-integrin biologic therapies in UC patients is associated with the signature of this antimicrobial macrophage population in a subset of patients. This study identified conserved and distinct features of intestinal inflammation between parts of the small and large intestine undergoing similar inflammation conditions.

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溃疡性结肠炎患者回肠肛门袋免疫细胞转录图谱

人们对人类肠道免疫系统如何明确地组织以应对炎症仍然知之甚少。在这里，我们使用单细胞RNA测序检查了患有回肠囊肛门吻合术或溃疡性结肠炎患者结肠黏膜的炎性肠病患者的固有层CD45 +造血细胞。我们确定了与炎症组织相关并在炎症组织中扩增的IL1B +抗菌巨噬细胞和FOXP3 + / BATF + T细胞，我们在IBD患者的其他scRNA-seq数据集中进一步进行了验证。相比于结肠，袋中CD8 + T细胞出乎意料地丰富。从单细胞RNA测序获得的细胞类型特异性标记物可用于从大量RNA测序数据集中推断代表性，它进一步暗示了表达IL1B的抗微生物巨噬细胞与S100A8 / A9钙卫蛋白，以及与细菌，拟杆菌和大肠埃希氏菌相关的炎症。最后，我们发现UC患者对抗整联蛋白生物疗法的无反应性与部分患者中该抗微生物巨噬细胞群的特征有关。这项研究确定了小肠和大肠中经历相似炎症条件的部分之间的肠道炎症的保守且独特的特征。我们发现在UC患者中对抗整合素生物疗法的无反应性与部分患者中该抗微生物巨噬细胞群的特征有关。这项研究确定了小肠和大肠中经历相似炎症条件的部分之间的肠道炎症的保守且独特的特征。我们发现在UC患者中对抗整合素生物疗法的无反应性与部分患者中该抗微生物巨噬细胞群的特征有关。这项研究确定了小肠和大肠中经历相似炎症条件的部分之间的肠道炎症的保守且独特的特征。