Development of a T(H)17 immune response during the induction of murine syngeneic graft-versus-host disease.
Development of a T(H)17 immune response during the induction of murine syngeneic graft-versus-host disease.
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DOI：
10.1016/j.cyto.2010.08.006
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发表时间：
2010-12
期刊：
影响因子：
3.8
通讯作者：
Bryson, J. Scott
中科院分区：
文献类型：
--
作者：
Brandon, J. Anthony;Jennings, C. Darrell;Kaplan, Alan M.;Bryson, J. Scott
同系移植物抗宿主病（SGVHD）在致死辐射、同系骨髓（BM）重建和免疫抑制剂环孢菌素A（CsA）21天疗程治疗后发展。SGVHD的临床症状在CsA后2-3周出现，结肠和肝脏出现炎症。以前，我们已经证明，CD 4 + T细胞和T辅助细胞1型细胞因子反应（TH 1）参与SGVHD相关肠道炎症的发展。最近的研究发现了一个额外的T细胞谱系，产生IL-17，被称为TH 17。有人认为，炎症性肠病是TH 17反应的结果，而不是TH 1反应。本研究旨在研究TH 17参与SGVHD相关结肠炎。在诱导SGVHD后，在对照和SGVHD动物中测量TH 17和TH 1细胞因子mRNA和蛋白的水平。进行体内细胞因子中和以确定原型TH 17细胞因子IL-17在疾病过程中的作用。我们发现在CsA诱导的小鼠SGVHD过程中，患病小鼠结肠内的TH 17和TH 1 mRNA和细胞因子均增加。给予抗小鼠IL-17 A mAb未改变病程。然而，IL-17 A的中和导致IL-17 F（一种相关家族成员）的产生增加，具有重叠范围的效应物活性。这些结果表明，在SGVHD的病理生理学中，在介导SGVHD发展的TH 17效应分子中存在冗余。
Syngeneic graft-versus-host disease (SGVHD) develops following lethal irradiation, reconstitution with syngeneic bone marrow (BM) and treatment with a 21 day course of the immunosuppressive agent cyclosporine A (CsA). Clinical symptoms of SGVHD appear 2-3 weeks post CsA with inflammation occurring in the colon and liver. Previously we have demonstrated that CD4+ T cells and a T helper cell type 1 cytokine response (TH1) are involved in the development of SGVHD associated intestinal inflammation. Studies have recently discovered an additional T cell lineage that produces IL-17 and is termed TH17. It has been suggested that inflammatory bowel disease is a result of a TH17 response rather than a TH1 response. This study was designed to investigate TH17 involvement in SGVHD-associated colitis. Following induction of SGVHD, the levels of TH17 and TH1 cytokine mRNA and protein were measured in control and SGVHD animals. In vivo cytokine neutralization was performed to determine the role of the prototypic TH17 cytokine, IL-17, in the disease process. We found that during CsA-induced murine SGVHD there was an increase in both TH17 and TH1 mRNA and cytokines within the colons of diseased mice. The administration of an anti-mouse IL-17A mAb did not alter the course of disease. However, neutralization of IL-17A resulted in an increased production of IL-17F, a related family member, with an overlapping range of effector activities. These results demonstrate that in the pathophysiology of SGVHD, there is a redundancy in the TH17 effector molecules that mediate the development of SGVHD.
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影响因子：
64.8
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