Distinct Alterations in the Composition of Mucosal Innate Lymphoid Cells in Newly Diagnosed and Established Crohn's Disease and Ulcerative Colitis
Distinct Alterations in the Composition of Mucosal Innate Lymphoid Cells in Newly Diagnosed and Established Crohn's Disease and Ulcerative Colitis
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DOI：
10.1093/ecco-jcc/jjy119
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发表时间：
2019-01-01
影响因子：
8
通讯作者：
Mjosberg, Jenny
中科院分区：
文献类型：
--
作者：
Forkel, Marianne;van Tol, Sophie;Mjosberg, Jenny
背景与目的：先天淋巴样细胞（Innate lymphoid cells， ILC）被认为在炎症性肠病（inflammatory bowel disease， IBD）中发挥作用。在这里，我们研究了不同的克罗恩病（CD）和溃疡性结肠炎（UC）患者的肠道活检和血液中的ILC区室，这些患者无论是新诊断的还是患病至少1年的。这种方法使我们能够同时研究IBD中ILC组成的时间、疾病特异性和组织特异性变化。方法：采用多参数流式细胞术分析血液和肠道活检中ILC亚群频率、表型和转录因子谱。采用溃疡性结肠炎内镜严重程度指数和克罗恩病简单内镜评分来判断内镜下疾病严重程度。结果：无论是CD患者还是UC患者，炎症组织中NKp44(+)ILC3的频率在诊断时就已经降低，并且与疾病严重程度相关。同时，在CD患者中ILC1的频率增加，而UC患者中ILC2的频率增加。然而，在已确诊的UC或CD患者中，ILC1和ILC2均升高。与炎症组织中的ILC组成相反，与非ibd对照组相比，非炎症组织或血液中的ILC没有变化。最后，在接受抗α (4) β(7)抗体治疗的患者中，外周血中ILC的频率保持不变。结论：我们报告了ILC组成根据诊断和疾病持续时间的共同和不同的变化。IBD中ILC组成的改变选择性地发生在肠道炎症部位。
Background and Aims: Innate lymphoid cells [ILC] have been suggested to play a role in inflammatory bowel disease [IBD]. Here, we investigated the ILC compartment in intestinal biopsies and blood from distinct patient groups with Crohn's disease [CD] and ulcerative colitis [UC], either newly diagnosed or with disease established for at least 1 year. This approach allowed us to simultaneously investigate temporal, disease-specific, and tissue-specific changes in ILC composition in IBD.Methods: ILC subset frequencies, phenotype, and transcription factor profile in blood and intestinal biopsies were investigated by multi-parameter flow cytometry analysis. Endoscopic disease severity was judged using the ulcerative colitis endoscopic index of severity and the simple endoscopic score for Crohn's disease.Results: The frequency of NKp44(+)ILC3 was decreased in inflamed tissue, both in patients with CD and those with UC, already at the time of diagnosis, and correlated with disease severity. Simultaneously, the frequency of ILC1 was increased in patients with CD, whereas the frequency of ILC2 was increased in patients with UC. However, in patients with established UC or CD, both ILC1 and ILC2 were increased. In contrast to the ILC composition in inflamed tissue, ILC in non-inflamed tissue or blood were unchanged compared with non-IBD controls. Finally, in patients undergoing treatment with an anti-alpha(4)beta(7) antibody the frequencies of ILC in peripheral blood remained unchanged.Conclusions: We report both shared and distinct changes in ILC composition depending on diagnosis and disease duration. The alterations in ILC composition in IBD occur selectively at inflamed sites in the gut.