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黏附分子-1 和肠道归巢 T 细胞在炎症性袋状黏膜中的表达。

Expression of MAdCAM-1 and Gut-homing T Cells in Inflamed Pouch Mucosa.

机构信息

Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, University of Amsterdam, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.

Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

J Crohns Colitis. 2021 Sep 25;15(9):1491-1499. doi: 10.1093/ecco-jcc/jjab041.

Abstract

BACKGROUND AND AIMS

Pouchitis is a common complication following formation of an ileal pouch-anal anastomosis [IPAA] after proctocolectomy for ulcerative colitis [UC]. Gut-specific lymphocyte trafficking mechanisms have been identified as players in the pathogenesis of UC. In the present study, we aimed to characterise the presence of lymphocyte subsets expressing gut-homing molecules in pouches and peripheral blood of UC patients with and without pouchitis.

METHODS

Biopsy samples and peripheral blood were collected from 29 patients with an IPAA [seven with active inflammation, 22 without inflammation]. Expression of adhesion molecule MAdCAM-1 was assessed using immunohistochemistry, and flow cytometry was used to characterise expression of integrin α4β7, C-chemokine receptor 9 [CCR9], and CD103 on T cell subsets.

RESULTS

MAdCAM-1 expression was significantly increased in case of active inflammation in the pouch. T cells expressing integrin α4β7 were abundant in the pouch mucosa, but the frequency of integrin α4β7-expressing T cells was decreased on CD4+ lymphocytes during inflammation. Co-expression of gut-homing markers CCR9 and α4β7 was more pronounced in biopsies compared with peripheral blood, but was not enhanced upon active inflammation.

CONCLUSIONS

Gut-homing T cells are abundant in pouch mucosa, but the classic hypothesis that the chronic inflammatory state is maintained by an accumulation of α4β7-expressing effector T cells is not supported by our data.

摘要

背景与目的

回肠储袋肛管吻合术(IPAA)后发生的 pouchitis 是溃疡性结肠炎(UC)患者行直肠结肠切除术的常见并发症。肠道特异性淋巴细胞迁移机制已被确定为 UC 发病机制中的参与者。在本研究中,我们旨在描述 pouchitis 患者和无 pouchitis 患者的 pouch 和外周血中表达肠道归巢分子的淋巴细胞亚群的存在情况。

方法

收集 29 例接受 IPAA 的患者(7 例有活动性炎症,22 例无炎症)的活检样本和外周血。使用免疫组织化学评估粘附分子 MAdCAM-1 的表达,使用流式细胞术分析整合素 α4β7、C 趋化因子受体 9(CCR9)和 CD103 在 T 细胞亚群上的表达。

结果

pouch 中有活动性炎症时,MAdCAM-1 的表达显著增加。整合素 α4β7 表达的 T 细胞在 pouch 黏膜中丰富,但在炎症期间 CD4+淋巴细胞上整合素 α4β7 表达的 T 细胞频率降低。与外周血相比,肠道归巢标志物 CCR9 和 α4β7 的共表达在活检中更为明显,但在活动性炎症时并未增强。

结论

肠道归巢 T 细胞在 pouch 黏膜中丰富,但我们的数据不支持慢性炎症状态是通过积累表达 α4β7 的效应 T 细胞维持的经典假说。

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