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

Histopathological Features of Inflammatory Bowel Disease are Associated With Different CD4+ T Cell Subsets in Colonic Mucosal Lamina Propria
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DOI:
10.1093/ecco-jcc/jjy116
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发表时间:
2018-12-01
影响因子:
8
通讯作者:
Ghosh, Subrata
Ghosh, Subrata
中科院分区:
医学1区
文献类型:
--
作者:
Gui, Xianyong;Li, Ji;Ghosh, Subrata

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背景资料:炎症性肠病[IBD]特别是由CD 4(+)辅助性和调节性T细胞的异常引起的,并且包括组织病理学慢性活动性小肠结肠炎,其特征反映了粘膜炎症的活动性和慢性性。方法:我们研究了溃疡性结肠炎(UC)和克罗恩病(CD)结肠黏膜CD 4(+)T细胞亚群[Th 1,Th 2,Th 17,Th 22和Treg]与黏膜组织学改变的相关性。流式细胞仪检测CD 4(+)T细胞亚群及计数。使用三种经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。结果:Treg细胞与ECAP A类活性及RHI评分相关。Treg细胞在粘膜中增加,尤其是在隐窝/表面上皮和固有层中有严重的嗜中性粒细胞浸润,并伴有基底浆细胞增多。Th 17细胞在固有层广泛中性粒细胞浸润的病例中也增加,而RORc(+)细胞在固有层严重淋巴浆细胞浸润的病例中增加。在UC和CD中,具有显著隐窝结构改变的粘膜具有增加的IL-22(+)和Th 22细胞。UC伴潘氏细胞化生者Th 17细胞比例较高。CD伴肉芽肿患者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。Th 17也与活动有关。相反,IL-22(+)细胞与CD的慢性化和肉芽肿形成相关。
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-gamma(+) 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.