CD73 is a phenotypic marker of effector memory Th17 cells in inflammatory bowel disease.

CD73 is a phenotypic marker of effector memory Th17 cells in inflammatory bowel disease.
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DOI:
10.1002/eji.201242623
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发表时间:
2012-11
影响因子:
5.4
通讯作者:
Robson, Simon C.
Robson, Simon C.
中科院分区:
医学3区
文献类型:
--
作者:
Doherty, Glen A.;Bai, Aiping;Hanidziar, Dusan;Longhi, Maria S.;Lawlor, Garrett O.;Putheti, Prabhakar;Csizmadia, Eva;Nowak, Martina;Cheifetz, Adam S.;Moss, Alan C.;Robson, Simon C.

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嘌呤能信号传导和相关的外核苷酸酶,如CD 39和CD 73,已经涉及炎症性肠病(IBD)的发病机制。已知CD 39是Treg记忆细胞标志物,在此我们确定IBD患者中CD 73 + CD 4 + T淋巴细胞的表型和功能。我们描述了活动性IBD患者外周血和肠固有层中CD 73 + CD 4 + T细胞水平升高。这些CD 73 + CD 4 + T细胞的功能表型通过基因表达、胞外酶活性和抑制性测定进一步确定。在活动性炎症期间,外周和固有层中的CD 73 + CD 4 + T细胞数量增加,在抗TNF治疗后恢复至基线水平。外周血CD 73 + CD 4 + T细胞主要表达CD 45 RO,并富含IL-17 A+细胞。与CD 73 − CD 4 + T细胞相比,CD 73 + CD 4+细胞群体表达更高水平的RORC、IL-17 A和TNF,以及更低水平的FOXP 3和/或CD 25。外周血CD 4 + T细胞的CD 73表达在TNF作用下增加,而在抗TNF单克隆抗体(英夫利西单抗)作用下减少。在体外,这些外周CD 73 + CD 4 + T细胞不抑制CD 25 −效应细胞的增殖,并表达更高水平的促炎标志物。我们的结论是,CD 73 + CD 4 + T细胞群在活动性IBD患者中富含T辅助细胞17型表型,可用于监测治疗期间的疾病活动。
Purinergic signaling and associated ectonucleotidases, such as CD39 and CD73, have been implicated in the pathogenesis of inflammatory bowel disease (IBD). CD39 is known to be a Treg memory cell marker, and here we determine the phenotype and function of CD73+CD4+ T lymphocytes in patients with IBD. We describe elevated levels of CD73+CD4+ T cells in the peripheral blood and intestinal lamina propria of patients with active IBD. The functional phenotype of these CD73+CD4+ T cells was further determined by gene expression, ecto-enzymatic activity, and suppressive assays. Increased numbers of CD73+CD4+ T cells in the periphery and lamina propria were noted during active inflammation, which returned to baseline levels following anti-TNF treatment. Peripheral CD73+CD4+ T cells predominantly expressed CD45RO, and were enriched with IL-17A+ cells. The CD73+CD4+ cell population expressed higher levels of RORC, IL-17A, and TNF, and lower levels of FOXP3 and/or CD25, than CD73−CD4+ T cells. Expression of CD73 by peripheral CD4+ T cells was increased by TNF, and decreased by an anti-TNF monoclonal antibody (infliximab). In vitro, these peripheral CD73+CD4+ T cells did not suppress proliferation of CD25− effector cells, and expressed higher levels of pro-inflammatory markers. We conclude that the CD73+CD4+ T-cell population in patients with active IBD are enriched with cells with a T-helper type 17 phenotype, and could be used to monitor disease activity during treatment.
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