Reduced Numbers and Proapoptotic Features of Mucosal-associated Invariant T Cells as a Characteristic Finding in Patients with Inflammatory Bowel Disease

Reduced Numbers and Proapoptotic Features of Mucosal-associated Invariant T Cells as a Characteristic Finding in Patients with Inflammatory Bowel Disease
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DOI:
10.1097/mib.0000000000000397
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发表时间:
2015-07-01
影响因子:
4.9
通讯作者:
Heike, Toshio
Heike, Toshio
中科院分区:
医学2区
文献类型:
--
作者:
Hiejima, Eitaro;Kawai, Tomoki;Heike, Toshio

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背景:粘膜相关不变T细胞(MAIT)是一种天然的T细胞,参与粘膜免疫的动态平衡,但其在炎症性肠病(IBD)中的作用尚不清楚。方法:采用流式细胞术对88例溃疡性结肠炎(UC)、68例克罗恩病(CD)和57例健康人外周血MAIT细胞进行计数。免疫组织化学染色显示,UC患者(n=5)、CD患者(n=10)、对照结肠(n=5)和小肠(n=9)组织中有MAIT细胞。此外,还检测了14例UC、15例CD患者和16例健康对照外周血中MAIT细胞活化的caspase的表达。结果:IBD患者外周血中MAIT细胞的数量明显少于健康对照组(P<0.0001)。UC和CD患者炎性肠黏膜中MAIT细胞的数量也低于对照组(P=0.0079和0.041)。UC和CD患者外周血中活化的表达caspase的MAIT细胞数明显高于正常对照组(P分别为0.0061和0.0075),提示IBD患者MAIT细胞数量减少与细胞凋亡率增加有关。此外,IBD患者的MAIT细胞也表现出促凋亡的特征。这些数据提示IBD患者中这些细胞的病理参与和治疗操作的可能性。
Background:Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in the homeostasis of mucosal immunity; however, their role in inflammatory bowel disease (IBD) is unclear.Methods:Flow cytometry was used to enumerate peripheral blood MAIT cells in 88 patients with ulcerative colitis (UC), 68 with Crohn's disease (CD), and in 57 healthy controls. Immunohistochemistry identified MAIT cells in intestinal tissue samples from patients with UC (n = 5) and CD (n = 10), and in control colon (n = 5) and small intestine (n = 9) samples. In addition, expression of activated caspases by MAIT cells in the peripheral blood of 14 patients with UC and 15 patients with CD, and 16 healthy controls was examined.Results:Peripheral blood analysis revealed that patients with IBD had significantly fewer MAIT cells than healthy controls (P < 0.0001). The number of MAIT cells in the inflamed intestinal mucosae of patients with UC and CD was also lower than that in control mucosae (P = 0.0079 and 0.041, respectively). The number of activated caspase-expressing MAIT cells in the peripheral blood of patients with UC and CD was higher than that in healthy controls (P = 0.0061 and 0.0075, respectively), suggesting that the reduced MAIT cell numbers in IBD are associated with an increased level of apoptosis among these cells.Conclusions:The number of MAIT cells in the peripheral blood and inflamed mucosae of patients with UC and CD was lower than that in non-IBD controls. Also, MAIT cells from patients with IBD exhibited proapoptotic features. These data suggest the pathological involvement and the potential for therapeutic manipulation of these cells in patients with IBD.