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Role of CMV chemokine receptor M33 in airway graft rejection in a mouse transplant model
Transplant Immunology ( IF 1.5 ) Pub Date : 2021-05-24 , DOI: 10.1016/j.trim.2021.101415
Isabella Hanka 1 , Thomas Stamminger 2 , Martina Ramsperger-Gleixner 1 , Annika V Kuckhahn 1 , Regina Müller 3 , Michael Weyand 1 , Christian Heim 1
Affiliation  

Background

Cytomegalovirus (CMV) infection is a risk factor for bronchiolitis obliterans (BO), one form of chronic lung allograft dysfunction (CLAD). The viral chemokine receptor M33 is essential for successful spread of murine CMV to host salivary glands. In the present study we investigated the impact of M33 on chronic airway rejection.

Methods

MHC I-mismatched tracheas of C·B10-H2b/LilMcdJ mice were transplanted into BALB/c (H2d) recipients and infected at different dates with wild type (WT) or M33-deleted (delM33) MCMV representing clinical settings of viral recipient (R)-donor (D)-serostatus: (D−/R+) or (D+/R-). Grafts were recovered for gene expression and histological / immunofluorescence analysis, respectively.

Results

Evaluations showed significantly increased signs of chronic rejection in WT-infected mice compared to uninfected allografts seen in lower epithelium/lamina propria-ratio (ELR) (ELR 0.46 ± 0.07 [WT post] vs. ELR 0.66 ± 0.10 [non-inf.]; p < 0.05). The rejection in delM33-infected groups was significantly reduced vs. WT-infected groups (0.67 ± 0.04 [delM33 post]; vs. WT post p < 0.05). Furthermore, decreased rejection was observed in WT pre-infected compared to post-infected groups (0.56 ± 0.08 [WT pre]; vs. WT post p < 0.05). CD8+ T cell infiltration was significantly higher in WT-post compared to the delM33 infected or non-infected allografts.

Conclusions

These data support the role of the CMV in accelerating CLAD. The deletion of chemokine receptor M33 leads to attenuated rejection.



中文翻译:

CMV趋化因子受体M33在小鼠移植模型气道移植排斥中的作用

背景

巨细胞病毒 (CMV) 感染是闭塞性细支气管炎 (BO) 的危险因素,这是一种慢性肺移植功能障碍 (CLAD)。病毒趋化因子受体 M33 对于鼠 CMV 成功传播到宿主唾液腺至关重要。在本研究中,我们调查了 M33 对慢性气道排斥反应的影响。

方法

将 C·B10-H2 b / LilMcdJ 小鼠的MHC I 错配气管移植到 BALB/c (H2 d ) 受体中,并在不同日期感染野生型 (WT) 或 M33 缺失 (delM33) MCMV,代表病毒的临床环境受体(R)-供体(D)-血清状态:(D-/R+)或(D+/R-)。分别回收移植物用于基因表达和组织学/免疫荧光分析。

结果

评估显示,与未感染的同种异体移植物相比,在 WT 感染的小鼠中慢性排斥的迹象显着增加,见于下上皮/固有层比率 (ELR)(ELR 0.46 ± 0.07 [WT post] vs. ELR 0.66 ± 0.10 [non-inf.] ; p  < 0.05)。与 WT 感染组相比,delM33 感染组的排斥显着降低(0.67 ± 0.04 [delM33 后];与 WT 后p  < 0.05)。此外,与感染后组相比,在感染前的 WT 中观察到排斥减少(0.56 ± 0.08 [WT 前];与 WT 后p  < 0.05)。与 delM33 感染或未感染的同种异体移植物相比,WT-post 中的CD8 + T 细胞浸润显着更高。

结论

这些数据支持 CMV 在加速 CLAD 中的作用。趋化因子受体 M33 的缺失会导致排斥反应减弱。

更新日期:2021-05-26
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