Xu Lei, Xiao Ting, Xu Ling, Zou Biao, Yao Wei
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Ultrasonography, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Pediatr Res. 2025 Mar 22. doi: 10.1038/s41390-025-03961-x.
Pediatric Crohn's disease (CD) is a chronic inflammatory bowel disorder that poses significant health risks to children. Although the precise etiology of CD remains elusive, further exploration is needed to identify diagnostic biomarkers and therapeutic targets.
This study utilized single-cell and bulk RNA sequencing data derived from ileal and colonic biopsy samples to explore the molecular mechanisms and cell types associated with CD, as well as to pinpoint potential biomarkers and therapeutic targets.
The results revealed a more pronounced alteration in both the quantity and functional state of neutrophils in the CD cohort compared to those with ulcerative colitis and healthy controls. Neutrophils were present in higher proportions in the CD group, primarily in an activated state, potentially correlating with the presence of deep ulcerations and inflammatory histopathological features. Additionally, neutrophil interactions with other cell types were markedly enhanced in the CD group, making neutrophils the dominant participants in cell-to-cell communications. Further analysis indicated a shift in neutrophil phenotype from pro-inflammatory and antimicrobial to tissue-repairing, which may contribute to the progression and exacerbation of CD.
IL1B, ICAM1, CXCL1, and CXCL9, primarily expressed in neutrophils, were potential biomarkers for CD. Neutrophils might be considered a potential target for pediatric CD.
This study demonstrated that patients with CD exhibited a greater proportion of activated neutrophils, with enhanced interactions between neutrophils and all other cell types, resulting in neutrophils contributing the most cell-cell interactions within the CD gut. Neutrophils in the CD gut transition from a pro-inflammatory and antibacterial phenotype to one that promotes tissue healing, potentially influencing the progression and exacerbation of CD. Neutrophils represent a promising therapeutic target in pediatric CD. Hub genes associated with CD, including IL1B, ICAM1, CXCL1, and CXCL9, are predominantly expressed in neutrophils, positioning them as promising diagnostic biomarkers for CD.
儿童克罗恩病（CD）是一种慢性炎症性肠病，对儿童健康构成重大风险。尽管CD的确切病因仍不清楚，但需要进一步探索以确定诊断生物标志物和治疗靶点。
本研究利用来自回肠和结肠活检样本的单细胞和批量RNA测序数据，探索与CD相关的分子机制和细胞类型，以及确定潜在的生物标志物和治疗靶点。
结果显示，与溃疡性结肠炎患者和健康对照相比，CD队列中的中性粒细胞数量和功能状态发生了更明显的改变。CD组中中性粒细胞的比例更高，主要处于激活状态，这可能与深度溃疡和炎症组织病理学特征的存在相关。此外，CD组中中性粒细胞与其他细胞类型的相互作用明显增强，使中性粒细胞成为细胞间通讯的主要参与者。进一步分析表明，中性粒细胞表型从促炎和抗菌转变为组织修复，这可能有助于CD的进展和加重。
主要在中性粒细胞中表达的IL1B、ICAM1、CXCL1和CXCL9是CD的潜在生物标志物。中性粒细胞可能被视为儿童CD的潜在治疗靶点。
本研究表明，CD患者表现出更高比例的激活中性粒细胞，中性粒细胞与所有其他细胞类型之间的相互作用增强，导致中性粒细胞在CD肠道内的细胞间相互作用中占比最大。CD肠道中的中性粒细胞从促炎和抗菌表型转变为促进组织愈合的表型，可能影响CD的进展和加重。中性粒细胞是儿童CD中一个有前景的治疗靶点。与CD相关的枢纽基因，包括IL1B、ICAM1、CXCL1和CXCL9，主要在中性粒细胞中表达，使其成为CD有前景的诊断生物标志物。
