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炎症性肠病的组织病理学特征与结肠黏膜固有层中不同的 CD4+T 细胞亚群有关。

Histopathological Features of Inflammatory Bowel Disease are Associated With Different CD4+ T Cell Subsets in Colonic Mucosal Lamina Propria.

机构信息

Department of Pathology and Laboratory Medicine, University of Calgary, and Calgary Laboratory Services, Calgary, Alberta, Canada.

Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada.

出版信息

J Crohns Colitis. 2018 Nov 28;12(12):1448-1458. doi: 10.1093/ecco-jcc/jjy116.

Abstract

BACKGROUND

Inflammatory bowel disease [IBD] results particularly from an aberrance of CD4+ helper and regulatory T cells and comprises histopathologically chronic active enterocolitis with features reflecting both activity and chronicity of mucosal inflammation. The exact immunological-histological correlation in IBD is not understood.

METHODS

We studied the correlation between colonic mucosal CD4+ T cell subsets [Th1, Th2, Th17, Th22 and Treg] and mucosal histological changes in ulcerative colitis [UC] and Crohn's disease [CD]. CD4+ T cell subtyping and enumeration were achieved by flow cytometry. Histological features were categorized and assessed semi-quantitatively using three validated histological scoring schemes [ECAP, RHI and D'Haens]. Correlations between prevalence [%] of CD4+ T cell subsets and histological scores were analysed.

RESULTS

Treg cells were correlated with ECAP category A [activity] as well as RHI scores. Treg cell were increased particularly in mucosa with severe neutrophilic infiltration in the cryptal/surface epithelium and in lamina propria, and with basal plasmacytosis. Th17 cells were also increased in cases with extensive neutrophil infiltrate in lamina propria, whereas RORc+ cells were increased in cases with severe lymphoplasmacytic infiltration in lamina propria. In both UC and CD, mucosa with marked crypt architectural alteration had increased IL-22+ and Th22 cells. UC with Paneth cell metaplasia had higher Th17 cells. CD with granuloma had increased IL-22+ and IL-22+IFN-γ+ cells.

CONCLUSIONS

The Treg subset appears to be associated with the overall severity of IBD histopathology, particularly with active inflammation. Th17 is also associated with activity. By contrast, IL-22+ cells are associated with chronicity and granuloma formation in CD.

摘要

背景

炎症性肠病(IBD)主要是由于 CD4+辅助性和调节性 T 细胞的异常而引起的,其组织病理学表现为慢性活动性结肠炎,具有反映黏膜炎症活动和慢性的特征。IBD 的确切免疫组织学相关性尚不清楚。

方法

我们研究了溃疡性结肠炎(UC)和克罗恩病(CD)结肠黏膜 CD4+T 细胞亚群(Th1、Th2、Th17、Th22 和 Treg)与黏膜组织学变化之间的相关性。通过流式细胞术进行 CD4+T 细胞亚群分型和计数。使用三种经过验证的组织学评分方案(ECAP、RHI 和 D'Haens)对组织学特征进行分类和半定量评估。分析 CD4+T 细胞亚群的流行率(%)与组织学评分之间的相关性。

结果

Treg 细胞与 ECAP 类别 A(活动期)以及 RHI 评分相关。Treg 细胞在黏膜中严重中性粒细胞浸润、隐窝/表面上皮和固有层以及基底浆细胞增多时增加。在固有层广泛中性粒细胞浸润的病例中,Th17 细胞也增加,而在固有层严重淋巴浆细胞浸润的病例中,RORc+细胞增加。在 UC 和 CD 中,具有明显隐窝结构改变的黏膜中,IL-22+和 Th22 细胞增加。具有潘氏细胞化生的 UC 中 Th17 细胞增加。具有肉芽肿的 CD 中,IL-22+和 IL-22+IFN-γ+细胞增加。

结论

Treg 亚群似乎与 IBD 组织病理学的总体严重程度相关,特别是与活动性炎症相关。Th17 也与活性相关。相比之下,IL-22+细胞与 CD 中的慢性和肉芽肿形成相关。

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