新诊断的炎症性肠病患者炎症肠道中与T细胞亚群相关的高内皮小静脉

C. S. Horjus Talabur Horje, C. Smids, J. Meijer, M. Groenen, M. Rijnders, E. V. van Lochem, P. Wahab
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引用次数: 17

摘要

炎症性肠病(IBD)患者初始和中枢记忆T淋巴细胞(TN和TCM)可浸润炎症性肠黏膜。这些亚群归巢到肠道可能是由于三级淋巴器官(TLOs)异位形成,其中含有高内皮小静脉(HEVs)。我们的目的是评估新诊断,未经治疗的IBD患者炎症肠粘膜中hev和TLOs的存在与TN和TCM淋巴细胞存在的关系。前瞻性纳入IBD患者(n = 39)和健康对照(n = 8)。分别对炎症和正常肠道的活检样本进行免疫组化分析,检测淋巴细胞(CD3/CD20)、血管(CD31)和外周淋巴结寻址蛋白(PNAd)表达(MECA‐79)。流式细胞术免疫分型鉴定TN和TCM淋巴细胞亚群。溃疡性结肠炎患者的炎症结肠中HEV数量较高[中位数为3.05 HEV/mm2;四分位间距(IQR) = 0-6·39)和回肠(1·40;0‐4·34),与健康对照组相比(均为0;p = 0·033)。高密度的结肠hev (HEVhigh)与炎症肠道中TN和TCM的浸润增加有关(中位数87%;IQR = 82-93%的T细胞群),而HEVlow患者(58%;38 - 81%;p = 0·003)。HEVhigh患者的结肠卵泡数量较高(中位数为0.54 /mm2;IQR 0.28 - 0.84),而HEVlow患者(0.25 /mm2;0·08-0·45;P = 0.031)和对照组(0.31 /mm2;0·23-0·45;p = 0·043)。在一个亚组患者中,滤泡外hev和TLOs的异位形成可能促进了IBD患者TN和TCM淋巴细胞向炎症肠道组织的归巢。
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High endothelial venules associated with T cell subsets in the inflamed gut of newly diagnosed inflammatory bowel disease patients
Naive and central memory T lymphocytes (TN and TCM) can infiltrate the inflamed gut mucosa in inflammatory bowel disease (IBD) patients. Homing of these subsets to the gut might be explained by ectopic formation of tertiary lymphoid organs (TLOs), containing high endothelial venules (HEVs). We aimed to evaluate the presence of HEVs and TLOs in inflamed intestinal mucosa of newly diagnosed, untreated IBD patients in relation to the presence of TN and TCM lymphocytes. IBD patients (n = 39) and healthy controls (n = 8) were included prospectively. Biopsy samples of inflamed and normal intestine, respectively, were analysed by immunohistochemistry for lymphocytes (CD3/CD20), blood vessels (CD31) and peripheral lymph node addressin (PNAd) expression (MECA‐79). TN and TCM lymphocyte subsets were identified by flow cytometric immunophenotyping. A higher number of HEVs was found in the inflamed colon of patients with ulcerative colitis [median 3·05 HEV/mm2; interquartile range (IQR) = 0–6·39] and ileum of Crohn's disease patients (1·40; 0‐4·34) compared to healthy controls (both 0; P = 0·033). A high density of colonic HEVs (HEVhigh) was associated with increased infiltration of TN and TCM in the inflamed gut (median 87%; IQR = 82–93% of T cell population), compared to HEVlow patients (58%; 38–81%; P = 0·003). The number of colonic follicles was higher in HEVhigh patients (median 0·54/mm2; IQR 0·28–0·84) compared to HEVlow patients (0·25/mm2; 0·08–0·45; P = 0·031) and controls (0·31/mm2; 0·23–0·45; P = 0·043). Increased homing of TN and TCM lymphocytes to inflamed gut tissue in IBD patients might be facilitated by ectopic formation of extrafollicular HEVs and TLOs in a subgroup of patients.
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