Bamias Giorgos, Martin Charles, Marini Marco, Hoang Sharon, Mishina Margarita, Ross William G, Sachedina Muhammadreza A, Friel Charles M, Mize James, Bickston Stephen J, Pizarro Theresa T, Wei Ping, Cominelli Fabio
Digestive Health Center of Excellence, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
J Immunol. 2003 Nov 1;171(9):4868-74. doi: 10.4049/jimmunol.171.9.4868.
TL1A is a novel TNF-like factor that acts as a costimulator of IFN-gamma secretion through binding to the death domain-containing receptor, DR3. The aim of this study was to test the hypothesis that TL1A may play an important role in inflammatory bowel disease (IBD) by functioning as a Th1-polarizing cytokine. The expression, cellular localization, and functional activity of TL1A and DR3 were studied in intestinal tissue specimens as well as isolated lamina propria mononuclear cells from IBD patients and controls. TL1A mRNA and protein expression was up-regulated in IBD, particularly in involved areas of Crohn's disease (CD; p < 0.03 vs control). TL1A production was localized to the intestinal lamina propria in macrophages and CD4(+) and CD8(+) lymphocytes from CD patients as well as in plasma cells from ulcerative colitis patients. The amount of TL1A protein and the number of TL1A-positive cells correlated with the severity of inflammation, most significantly in CD. Increased numbers of immunoreactive DR3-positive T lymphocytes were detected in the intestinal lamina propria from IBD patients. Addition of recombinant human TL1A to cultures of PHA-stimulated lamina propria mononuclear from CD patients significantly augmented IFN-gamma production by 4-fold, whereas a minimal effect was observed in control patients. Our study provides evidence for the first time that the novel cytokine TL1A may play an important role in a Th1-mediated disease such as CD.
TL1A是一种新型的肿瘤坏死因子样因子，它通过与含死亡结构域的受体DR3结合，作为γ干扰素分泌的共刺激因子。本研究的目的是检验以下假设：TL1A可能作为一种Th1极化细胞因子，在炎症性肠病（IBD）中发挥重要作用。我们对IBD患者和对照者的肠道组织标本以及分离的固有层单核细胞中TL1A和DR3的表达、细胞定位及功能活性进行了研究。IBD患者中TL1A的mRNA和蛋白表达上调，尤其是在克罗恩病（CD）的病变区域（与对照相比，p < 0.03）。TL1A由CD患者的巨噬细胞、CD4(+)和CD8(+)淋巴细胞以及溃疡性结肠炎患者的浆细胞在肠道固有层中产生。TL1A蛋白的量和TL1A阳性细胞的数量与炎症严重程度相关，在CD中最为显著。在IBD患者的肠道固有层中检测到免疫反应性DR3阳性T淋巴细胞数量增加。将重组人TL1A添加到CD患者经PHA刺激的固有层单核细胞培养物中，可使γ干扰素产生显著增加4倍，而在对照患者中观察到的影响极小。我们的研究首次为新型细胞因子TL1A可能在诸如CD这种Th1介导的疾病中发挥重要作用提供了证据。
