並列タイトル等Persistent reduction of mucosal-associated invariant T cells in primary biliary cholangitis
原発性胆汁性胆管炎における粘膜関連インバリアントT細胞の検討
一般注記Background & Aim: Mucosal-associated invariant T (MAIT) cells constitute a novel subset of innate-like T-lymphocytes characterized by a semi-invariant T-cell receptor repertoire capable of recognizing bacterial products. Considering the abundance of MAIT cells in the liver and the possible association between bacterial infections and primary biliary cholangitis (PBC), we aimed to analyze the involvement of MAIT cells in the immunopathogenesis of PBC. Methods: Peripheral blood and liver biopsy specimens were collected from 25 patients with PBC and 19 patients with chronic viral hepatitis. Surgically removed liver tissues distant from tumors in patients with metastatic liver tumors were used as controls. Mononuclear cells were separated using Ficoll-gradient, and the expression of various markers was investigated by flow cytometry. Cytokine production was investigated using blood MAIT cells after stimulation by anti-CD3/CD28-coupled beads with/without interleukin-7 (IL-7). Results: MAIT cells were significantly reduced in both the blood and liver of PBC patients compared with those in controls. MAIT cells in the blood of PBC patients expressed significantly lower levels of activation markers and IL-7 receptor. Moreover, MAIT cells in the blood of PBC patients showed impaired production of cytokines, especially tumor necrosis factor-α, after in vitro stimulation with IL-7. Interestingly, even after biochemical responses were achieved by ursodeoxycholic acid (UDCA) treatment, the frequencies of MAIT cells did not fully recover to normal levels. Conclusions: These findings suggested that MAIT cells were activated, exhausted and persistently depleted in PBC patients even after UDCA treatment, possibly as a consequence of persistent liver inflammation.
学位の種類: 博士（医学）. 報告番号: 甲第4382号. 学位記番号: 新大院博（医）甲第781号. 学位授与年月日: 平成30年3月23日
Journal of Gastroenterology and Hepatology. Article first published online: 21 December 2017.
新大院博（医）甲第781号
DOIinfo:doi/10.1111/jgh.14076
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