破译主要组织相容性复合体、肠道微生物组和代谢物在急性移植物抗宿主病发病机制中的作用

IF 2.2 4区 医学 Q3 HEMATOLOGY
Valentin Wenger , Robert Zeiser
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引用次数: 0

摘要

异体造血干细胞移植是现代血液病治疗的基石,但其疗效却因急性移植物抗宿主病(Graft-versus-Host Disease)而大打折扣。在急性移植物抗宿主病中,调理方案引起的上皮损伤导致损伤和病原体相关分子模式的释放,进而引发异体反应性供体T细胞的激活,最终导致健康组织的破坏。主要组织相容性复合体分型和使用组织特异性主要组织相容性复合体缺失的临床前研究的进展,阐明了造血细胞和非造血细胞对急性移植物抗宿主病病理生理学的贡献。与此同时,高通量测序技术使研究人员认识到肠道微生物组和新发现的代谢物对急性移植物抗宿主病病理生理学的重要影响。在这篇综述中,我们将讨论主要组织相容性复合物表达对造血细胞和非造血细胞的影响、对肠道微生物组的影响以及导致急性移植物抗宿主病的代谢改变。我们希望将这些发现结合起来,解开急性移植物抗宿主病的复杂性,最终为开发新的、更有效的患者治疗方案铺平道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Deciphering the role of the major histocompatibility complex, the intestinal microbiome and metabolites in the pathogenesis of acute graft-versus-host disease

Allogeneic hematologic stem cell transplantation is a cornerstone in modern hematological treatment, yet its efficacy is compromised by acute Graft-versus-Host Disease. In acute Graft-versus-Host Disease, conditioning regimen induced epithelial damage leads to release of damage and pathogen associated molecular patters which in turns triggers activation of alloreactive donor T cells, ultimately resulting in destruction of healthy tissue. Advances in major histocompatibility complex typing and preclinical studies using tissue specific major histocompatibility complex deletion have illuminated the contributions of both, hematopoietic and non-hematopoietic cells to acute Graft-versus-Host Disease pathophysiology. Concurrently, high-throughput sequencing techniques have enabled researchers to recognize the significant impact of the intestinal microbiome and newly discovered metabolites in the pathophysiology of acute Graft-versus-Host Disease. In this review, we discuss the implications of major histocompatibility complex expression on hematopoietic and non-hematopoietic cells, the effect on the intestinal microbiome and the metabolic alterations that contribute to acute Graft-versus-Host Disease. By combining these findings, we hope to untangle the complexity of acute Graft-versus-Host Disease, ultimately paving the way for the development of novel and more effective treatmen options in patients.

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来源期刊
CiteScore
4.20
自引率
0.00%
发文量
42
审稿时长
35 days
期刊介绍: Best Practice & Research Clinical Haematology publishes review articles integrating the results from the latest original research articles into practical, evidence-based review articles. These articles seek to address the key clinical issues of diagnosis, treatment and patient management. Each issue follows a problem-orientated approach which focuses on the key questions to be addressed, clearly defining what is known and not known, covering the spectrum of clinical and laboratory haematological practice and research. Although most reviews are invited, the Editor welcomes suggestions from potential authors.
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