活化的 HLA-DR+CD38+ Th1/17 效应细胞可将克罗恩病相关性肛周瘘与隐腺体瘘区分开来。

IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Inflammatory Bowel Diseases Pub Date : 2024-11-04 DOI:10.1093/ibd/izae103
Laura F Ouboter, Ciska Lindelauf, Qinyue Jiang, Mette Schreurs, Tamim R Abdelaal, Sietse J Luk, Marieke C Barnhoorn, Willem E Hueting, Ingrid J Han-Geurts, Koen C M J Peeters, Fabian A Holman, Frits Koning, Andrea E van der Meulen-de Jong, Maria Fernanda Pascutti
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引用次数: 0

摘要

背景:肛周瘘是克罗恩病(CD)的一种致残性并发症。由于不明原因,CD 相关性瘘管一般比隐性腺瘘管(非 CD 相关性)更难治疗。了解免疫细胞的结构是为 CD 相关性瘘管开发更有效疗法的第一步。在这项工作中,我们通过高维分析确定了两种类型肛周瘘中疾病相关免疫细胞的组成和空间定位特征:我们应用单细胞质谱(scMC)、光谱流式细胞仪(SFC)和成像质谱(IMC)分析了CD相关性肛周瘘和隐窝瘘中的免疫区。用 scMC 分析了一个探索性队列(CD 性瘘管,n = 10;非 CD 性瘘管,n = 5),以揭示与疾病相关的免疫细胞类型。对第二个瘘管队列(CD,n = 10;非 CD,n = 11)进行了 SFC 分析,以对与疾病相关的 T 辅助细胞(Th)进行全面表型。对第三个队列(CD,n = 5)使用 IMC 研究相关免疫细胞亚群的空间分布/相互作用:我们的分析表明,与隐窝瘘相比,CD相关性瘘中具有Th1/17表型的活化HLA-DR+CD38+效应CD4+ T细胞明显增多。这些细胞具有增殖、调节和分化的特征,也存在于血液中,并与瘘道中的其他 CD4+ T 细胞、CCR6+ B 细胞和巨噬细胞共定位:总之,增殖的活化HLA-DR+CD38+效应Th1/17细胞可区分CD相关性肛瘘和隐腺体性肛周瘘,是区分这两种肛瘘类型的理想血液生物标志物。以HLA-DR和CD38表达的CD4+ T细胞为靶点可能为CD相关性肛瘘提供一种潜在的新治疗策略。
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Activated HLA-DR+CD38+ Effector Th1/17 Cells Distinguish Crohn's Disease-associated Perianal Fistulas from Cryptoglandular Fistulas.

Background: Perianal fistulas are a debilitating complication of Crohn's disease (CD). Due to unknown reasons, CD-associated fistulas are in general more difficult to treat than cryptoglandular fistulas (non-CD-associated). Understanding the immune cell landscape is a first step towards the development of more effective therapies for CD-associated fistulas. In this work, we characterized the composition and spatial localization of disease-associated immune cells in both types of perianal fistulas by high-dimensional analyses.

Methods: We applied single-cell mass cytometry (scMC), spectral flow cytometry (SFC), and imaging mass cytometry (IMC) to profile the immune compartment in CD-associated perianal fistulas and cryptoglandular fistulas. An exploratory cohort (CD fistula, n = 10; non-CD fistula, n = 5) was analyzed by scMC to unravel disease-associated immune cell types. SFC was performed on a second fistula cohort (CD, n = 10; non-CD, n = 11) to comprehensively phenotype disease-associated T helper (Th) cells. IMC was used on a third cohort (CD, n = 5) to investigate the spatial distribution/interaction of relevant immune cell subsets.

Results: Our analyses revealed that activated HLA-DR+CD38+ effector CD4+ T cells with a Th1/17 phenotype were significantly enriched in CD-associated compared with cryptoglandular fistulas. These cells, displaying features of proliferation, regulation, and differentiation, were also present in blood, and colocalized with other CD4+ T cells, CCR6+ B cells, and macrophages in the fistula tracts.

Conclusions: Overall, proliferating activated HLA-DR+CD38+ effector Th1/17 cells distinguish CD-associated from cryptoglandular perianal fistulas and are a promising biomarker in blood to discriminate between these 2 fistula types. Targeting HLA-DR and CD38-expressing CD4+ T cells may offer a potential new therapeutic strategy for CD-related fistulas.

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来源期刊
Inflammatory Bowel Diseases
Inflammatory Bowel Diseases 医学-胃肠肝病学
CiteScore
9.70
自引率
6.10%
发文量
462
审稿时长
1 months
期刊介绍: Inflammatory Bowel Diseases® supports the mission of the Crohn''s & Colitis Foundation by bringing the most impactful and cutting edge clinical topics and research findings related to inflammatory bowel diseases to clinicians and researchers working in IBD and related fields. The Journal is committed to publishing on innovative topics that influence the future of clinical care, treatment, and research.
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