Expression of chemokines in GVHD target organs is influenced by conditioning and genetic factors and amplified by GVHR
Expression of chemokines in GVHD target organs is influenced by conditioning and genetic factors and amplified by GVHR
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DOI：
10.1016/j.bbmt.2006.02.005
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发表时间：
2006-06-01
影响因子：
4.3
通讯作者：
Sykes, Megan
中科院分区：
文献类型：
--
作者：
Mapara, Markus Y.;Leng, Corinna;Sykes, Megan
移植物抗宿主病（GVHD）是异基因造血细胞移植后最重要的临床问题。由于趋化因子诱导的促炎性条件化治疗可能会促进T细胞迁移到GVHD靶组织，我们解决了条件化对GVHD靶器官中趋化因子表达的影响。结果表明：（1）在GVHD相关T细胞浸润之前，预处理可导致GVHD靶器官中趋化因子的快速和短暂上调;（2）预处理强度和小鼠品系影响GVHD靶器官中趋化因子的表达;（3）与同基因骨髓移植相比，异基因骨髓移植导致清髓预处理后GVHD靶器官中趋化因子表达显著扩增。这也反映在血清和结肠中测量的趋化因子蛋白表达。肠道显示出对调节强度的最大敏感性，并且影响辅助性T细胞1型的趋化因子（例如，干扰素γ诱导蛋白10 [CXCL 10]）在调节后和GVHD期间在那里表达最强烈。然而，GVHD的严重程度在CXCR 3（+/+）或CXCR 3（-/-）脾细胞的受体之间没有显著差异，表明该趋化因子途径不起关键作用。总之，我们的数据表明，调节和受体菌株影响GVHD靶器官中的趋化因子表达，并且GVH同种异体反应性显著放大这种表达，从而促成与组织GVHD相关的炎症级联反应。(C)2006年美国血液和骨髓移植学会。
Graft-versus-host disease (GVHD) is the most significant clinical problem that arises after allogeneic hematopoietic cell transplantation. Because chemokines induced by proinflammatory conditioning treatment may promote T-cell migration into GVHD target tissues, we addressed the influence of conditioning on chemokine expression in GVHD target organs. Our results showed that (1) conditioning leads to rapid and transient chemokine upregulation in GVHD target tissues before the time of GVHD-associated T-cell infiltration; (2) conditioning intensity and mouse strain influence chemokine expression in GVHD target organs; and (3) compared with syngeneic bone marrow transplantation, allogeneic bone marrow transplantation led to marked amplification of chemokine expression in GVHD target organs after myeloablative conditioning. This is also reflected by chemokine protein expression that is measured in the serum and colon. Intestines showed the greatest sensitivity to conditioning intensity, and chemokines affecting T-helper type 1 cells (eg, interferon gamma-inducible protein 10 [CXCL10]) were most strongly expressed there after conditioning and during GVHD. However, severity of GVHD was not significantly different between recipients of CXCR3(+/+) or CXCR3(-/-) splenocytes, indicating that this chemokine pathway does not play a critical role. In summary, our data show that conditioning and recipient strain influence chemokine expression in GVHD target organs and that GVH alloreactivity markedly amplifies this expression, thus contributing to the inflammatory cascade associated with tissue GVHD. (C) 2006 American Society for Blood and Marrow Transplantation.