New insight into pathophysiology and treatment of GVHD
New insight into pathophysiology and treatment of GVHD
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DOI：
10.7889/tct-22-001
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Takahide Ara;D. Hashimoto
中科院分区：
文献类型：
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作者：
Takahide Ara;D. Hashimoto
紧密连接分子如claudin-4的表达在GVHD中也减少，导致肠上皮屏障功能的破坏。GLP-2可增强GVHD中claudin-4的表达，并可能改善肠屏障功能。DAMP，损伤相关分子模式; GLP-2，胰高血糖素样肽2; IFN-γ，干扰素-γ; 3分子模式;摘要移植物抗宿主病（GVHD）是异基因造血干细胞移植（allo-SCT）后潜在的危及生命的并发症;使用免疫抑制剂（如钙调磷酸酶抑制剂）预防GVHD对allo-SCT的成功至关重要。然而，严重的免疫抑制可导致肿瘤复发和感染并发症。因此，有必要开发一种新的管理策略，不依赖于免疫抑制剂的GVHD。新出现的证据表明，存在组织特异性机制来维持组织稳态以对抗由免疫应答和炎症引起的损伤。由于预处理方案和/或GVHD，这些机制在allo-SCT后被破坏。这些机制的损伤可能导致GVHD的发生、加重和难治。在这篇综述中，我们总结了最近的研究结果有关的组织内在机制，维持组织稳态，重点是肠道。（Japanese Journal of Transplantation and Cellular Therapy 11（2）：90-100，2022）
The expression of tight junction molecules such as claudin-4 are also reduced in GVHD, resulting in disruption of intestinal epithelial barrier function. GLP-2 enhances the expression of claudin-4 and possibly improves the intestinal barrier function in GVHD. DAMP, damage-associated molecular pattern; GLP-2, Glucagon-like peptide 2; IFN-γ, interferon-γ; 3 molecular pattern; Abstract Graft-versus-host disease（GVHD）is a potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation（allo-SCT）; GVHD prophylaxis using immunosuppressants, such as calcineurin inhibitors, is essential for the success of allo-SCT. However, profound immunosuppression can lead to tumor relapse and infectious complications. Therefore, it is necessary to develop a novel management strategy that does not rely on immunosuppressants for GVHD. Emerging evidence has demonstrated that there are tissue-specific mechanisms that maintain tissue homeostasis against damage caused by immune response and inflammation. These mechanisms are disrupted after allo-SCT due to conditioning regimens and／or GVHD. Moreover, it is also suggested that the impairment of these mechanisms may lead to the development, exacerbation, and refractoriness of GVHD. In this review, we summarize recent findings pertaining to tissue-intrinsic mechanisms that maintain tissue homeostasis, with a focus on the intestine.（Japanese Journal of Transplantation and Cellular Therapy 11（2）: 90—100, 2022.）