Host MyD88 signaling protects against acute graft-versus-host disease after allogeneic bone marrow transplantation
Host MyD88 signaling protects against acute graft-versus-host disease after allogeneic bone marrow transplantation
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宿主 MyD88 信号传导可预防同种异体骨髓移植后的急性移植物抗宿主病
DOI：
10.1111/cei.13215
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发表时间：
2018
影响因子：
4.6
通讯作者：
Zhou P
中科院分区：
文献类型：
--
作者：
Xing S;Zhang X;Liu JH;Huang X;Zhou P
最近的实验策略，以减少移植物抗宿主病（GVHD）主要集中在修改先天免疫。Toll样受体（TLR）驱动的髓样分化初级应答88（MyD 88）依赖性信号传导途径启动适应性免疫功能对于GVHD的发病机制也至关重要。本研究旨在阐明宿主MyD 88在主要组织相容性复合物完全不匹配的异基因骨髓移植（BMT）后急性GVHD发生中的作用。当骨髓清除的BALB/c MyD 88敲除受体移植C57 BL/6（B6）供体细胞时，它们比野生型（WT）BALB/c宿主发生显著更严重的GVHD。MyD 88-/-小鼠发病率和死亡率的增加与GVHD靶器官中脂多糖和炎性细胞因子的血清水平升高相关。此外，与WT BMT受者相比，MyD 88缺陷导致供体T细胞扩增增加和更多的供体CD 11 c+细胞肠浸润凋亡细胞，但肠上皮细胞增殖减少。MyD 88-/-小鼠上皮细胞中紧密连接mRNA的表达减少，表明MyD 88有助于肠道完整性。WT小鼠GVHD靶器官中考克斯-2的表达在诱导GVHD后明显增加，但MyD 88缺陷明显抑制这种表达。目前的研究结果表明，宿主MyD 88在同种异体BMT后预防GVHD中具有意想不到的作用。
Recent experimental strategies to reduce graft-versus-host disease (GVHD) have focused largely on modifying innate immunity. Toll-like receptor (TLR)-driven myeloid differentiation primary response 88 (MyD88)-dependent signalling pathways that initiate adaptive immune function are also critical for the pathogenesis of GVHD. This study aimed to delineate the role of host MyD88 in the development of acute GVHD following fully major histocompatibility complex-mismatched allogeneic bone mar-row transplantation (BMT). When myeloablated BALB/c MyD88 knock-out recipients were transplanted with C57BL/6 (B6) donor cells, they developed significantly more severe GVHD than wild-type (WT) BALB/c hosts. The increased morbidity and mortality in MyD88–/– mice correlated with in-creased serum levels of lipopolysaccharide and elevated inflammatory cytokines in GVHD target organs. Additionally, MyD88 deficiency in BMT recipients led to increased donor T cell expansion and more donor CD11c+ cell intestinal infiltration with apoptotic cells but reduced proliferation of intestinal epithelial cells compared with that in WT BMT recipients. De-creased expression of tight junction mRNA in epithelial cells of MyD88–/– mice suggested that MyD88 contributes to intestinal integrity. Cox-2 ex-pression in the GVHD-targeted organs of WT mice is increased upon GVHD induction, but this enhanced expression was obviously inhibited by MyD88 deficiency. The present findings demonstrate an unexpected role for host MyD88 in preventing GVHD after allogeneic BMT.