Differential Effects of Gut-Homing Molecules CC Chemokine Receptor 9 and Integrin-β7 during Acute Graft-versus-Host Disease of the Liver.

Differential Effects of Gut-Homing Molecules CC Chemokine Receptor 9 and Integrin-β7 during Acute Graft-versus-Host Disease of the Liver.
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肠道归巢分子 CC 趋化因子受体 9 和整合素-β7 在肝脏急性移植物抗宿主病中的不同作用

DOI:
10.1016/j.bbmt.2015.08.038
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发表时间:
2015
期刊:
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子:
--
通讯作者:
Koenecke C
Koenecke C
中科院分区:
--
文献类型:
--
作者:
Schreder A;Moschovakis GL;Halle S;Schlue J;Lee CW;Schippers A;David S;Bernhardt G;Ganser A;Pabst O;Förster R;Koenecke C

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同种异体供体T细胞的归巢是骨髓移植(BMT)后急性移植物抗宿主病(GVHD)发展的必要条件。在这项研究中,我们发现在BMT受体中,由于T细胞或其配体MAdCAM-1上整合素-β7缺乏而导致的T细胞归巢改变有助于实验性GVHD的病理生理。相比之下,供体T细胞缺乏CC趋化因子受体9会改变组织归巢,但不会影响GVHD的存活。我们进一步证明,MAdCAM-1在肝小鼠GVHD以及活动性肝GVHD患者中异常表达。然而,供体T细胞在肠道而非肝脏的浸润依赖于MAdCAM-1的表达,这表明供体T细胞的归巢和/或滞留取决于依赖于GVHD靶组织的不同分子途径。
Homing of allogeneic donor T cells to recipient tissue is imperative for the development of acute graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In this study we show that alteration of T cell homing due to integrin-β7 deficiency on T cells or its ligand MAdCAM-1 in BMT recipients contributes to the pathophysiology of experimental GVHD. In contrast, lack of CC chemokine receptor 9 on donor T cells alters tissue homing but does not impact GVHD survival. We further demonstrate that MAdCAM-1 is aberrantly expressed in hepatic murine GVHD as well as in patients with active liver GVHD. However, infiltration of donor T cells in gut but not liver was dependent of MAdCAM-1 expression, indicating, that homing and/or retention of donor T cells rests on divergent molecular pathways depending on the GVHD target tissue.
人粘膜地址素细胞粘附分子-1优先在肠道和相关淋巴组织中表达。
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