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Fibrotic progression from acute cellular rejection is dependent on secondary lymphoid organs in a mouse model of chronic lung allograft dysfunction.急性细胞排斥反应导致的纤维化进展依赖于慢性肺移植功能障碍小鼠模型中的次级淋巴器官。
Am J Transplant. 2024 Jun;24(6):944-953. doi: 10.1016/j.ajt.2024.02.020. Epub 2024 Feb 23.
2
Spectrum of chronic lung allograft pathology in a mouse minor-mismatched orthotopic lung transplant model.慢性肺移植物病谱在小鼠次要匹配原位肺移植模型中的表现。
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Rejection of tracheal allograft by intrapulmonary lymphoid neogenesis in the absence of secondary lymphoid organs.肺内淋巴样新生导致的气管同种异体移植物排斥，而无次级淋巴器官参与。
Transplantation. 2012 Jun 27;93(12):1212-20. doi: 10.1097/TP.0b013e318250fbf5.
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A B cell-dependent pathway drives chronic lung allograft rejection after ischemia-reperfusion injury in mice.B 细胞依赖性途径驱动小鼠缺血再灌注损伤后慢性肺移植排斥反应。
Am J Transplant. 2019 Dec;19(12):3377-3389. doi: 10.1111/ajt.15550. Epub 2019 Aug 26.
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Lymphotoxin β receptor and tertiary lymphoid organs shape acute and chronic allograft rejection.淋巴毒素β受体和三级淋巴器官塑造急性和慢性同种异体移植排斥反应。
JCI Insight. 2024 Jul 2;9(15):e177555. doi: 10.1172/jci.insight.177555.
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Asialo GM1 positive CD8+ T cells induce skin allograft rejection in the absence of the secondary lymphoid organs.去唾液酸GM1阳性CD8 + T细胞在无次级淋巴器官的情况下诱导皮肤同种异体移植排斥反应。
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The role of recipient derived interleukin-17A in a murine orthotopic lung transplant model of restrictive chronic lung allograft dysfunction.受体来源的白细胞介素-17A在限制性慢性肺移植功能障碍小鼠原位肺移植模型中的作用。
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Macrophage subpopulations and their impact on chronic allograft rejection versus graft acceptance in a mouse heart transplant model.巨噬细胞亚群及其对慢性移植排斥反应与移植物接受的影响在小鼠心脏移植模型中的作用。
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Recipient-derived EDA fibronectin promotes cardiac allograft fibrosis.供体来源的 EDA 纤维连接蛋白促进心脏移植物纤维化。
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HDAC6-specific inhibitor suppresses Th17 cell function via the HIF-1α pathway in acute lung allograft rejection in mice.组蛋白去乙酰化酶 6 特异性抑制剂通过 HIF-1α 通路抑制小鼠急性肺移植排斥反应中的 Th17 细胞功能。
Theranostics. 2020 May 21;10(15):6790-6805. doi: 10.7150/thno.44961. eCollection 2020.

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NKG2D blockade impairs tissue-resident memory T cell accumulation and reduces chronic lung allograft dysfunction.NKG2D阻断会损害组织驻留记忆T细胞的积累，并减少慢性肺移植功能障碍。
JCI Insight. 2025 Feb 24;10(4):e184048. doi: 10.1172/jci.insight.184048.
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Chronic Lung Allograft Dysfunction: Clinical Manifestations and Immunologic Mechanisms.慢性肺移植功能障碍：临床表现与免疫机制
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Preemptive treatment of de novo donor-specific antibodies in lung transplant patients reduces subsequent risk of chronic lung allograft dysfunction or death.预先治疗肺移植患者的新型供体特异性抗体可降低随后发生慢性肺移植物功能障碍或死亡的风险。
Am J Transplant. 2023 Apr;23(4):559-564. doi: 10.1016/j.ajt.2022.12.019. Epub 2023 Jan 19.
2
Primary graft dysfunction grade 3 following pediatric lung transplantation is associated with chronic lung allograft dysfunction.儿童肺移植后发生 3 级原发性移植物功能障碍与慢性肺移植物功能障碍有关。
J Heart Lung Transplant. 2023 May;42(5):669-678. doi: 10.1016/j.healun.2022.12.014. Epub 2022 Dec 27.
3
Delivery of costimulatory blockade to lymph nodes promotes transplant acceptance in mice.共刺激阻断剂递送至淋巴结可促进小鼠移植耐受。
J Clin Invest. 2022 Dec 15;132(24):e159672. doi: 10.1172/JCI159672.
4
Risk factors and outcomes of non-tuberculous mycobacteria infection in lung transplant recipients: A systematic review and meta-analysis.肺移植受者中非结核分枝杆菌感染的危险因素和结局：系统评价和荟萃分析。
J Heart Lung Transplant. 2023 Feb;42(2):264-274. doi: 10.1016/j.healun.2022.10.004. Epub 2022 Oct 12.
5
Recipient Comorbidities for Prediction of Primary Graft Dysfunction, Chronic Allograft Dysfunction and Survival After Lung Transplantation.肺移植后原发性移植物功能障碍、慢性移植物功能障碍和生存的受体合并症预测。
Transpl Int. 2022 Jun 29;35:10451. doi: 10.3389/ti.2022.10451. eCollection 2022.
6
Cytomegalovirus Infection Is Associated with Development of Chronic Lung Allograft Dysfunction.巨细胞病毒感染与慢性肺移植功能障碍的发生有关。
Lung. 2022 Aug;200(4):513-522. doi: 10.1007/s00408-022-00551-0. Epub 2022 Jul 6.
7
Perioperative diabetes mellitus affects the outcomes of lung transplant recipients.围手术期糖尿病会影响肺移植受者的预后。
Eur J Cardiothorac Surg. 2022 Jun 15;62(1). doi: 10.1093/ejcts/ezac344.
8
The Role of Intra-Patient Variability of Tacrolimus Drug Concentrations in Solid Organ Transplantation: A Focus on Liver, Heart, Lung and Pancreas.他克莫司药物浓度的患者内变异性在实体器官移植中的作用：聚焦于肝脏、心脏、肺和胰腺
Pharmaceutics. 2022 Feb 8;14(2):379. doi: 10.3390/pharmaceutics14020379.
9
The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-eighth adult lung transplantation report - 2021; Focus on recipient characteristics.国际心肺移植学会国际胸器官移植登记处：第三十八次成人肺移植报告-2021；关注受者特征。
J Heart Lung Transplant. 2021 Oct;40(10):1060-1072. doi: 10.1016/j.healun.2021.07.021. Epub 2021 Jul 31.
10
Humoral immune responses mediate the development of a restrictive phenotype of chronic lung allograft dysfunction.体液免疫反应介导慢性肺移植功能障碍限制性表型的发展。
JCI Insight. 2020 Dec 3;5(23):136533. doi: 10.1172/jci.insight.136533.

急性细胞排斥反应导致的纤维化进展依赖于慢性肺移植功能障碍小鼠模型中的次级淋巴器官。

Fibrotic progression from acute cellular rejection is dependent on secondary lymphoid organs in a mouse model of chronic lung allograft dysfunction.

机构信息

Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.

Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

出版信息

Am J Transplant. 2024 Jun;24(6):944-953. doi: 10.1016/j.ajt.2024.02.020. Epub 2024 Feb 23.

DOI:10.1016/j.ajt.2024.02.020
PMID:38403187
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11144565/
Abstract

Chronic lung allograft dysfunction (CLAD) remains one of the major limitations to long-term survival after lung transplantation. We modified a murine model of CLAD and transplanted left lungs from BALB/c donors into B6 recipients that were treated with intermittent cyclosporine and methylprednisolone postoperatively. In this model, the lung allograft developed acute cellular rejection on day 15 which, by day 30 after transplantation, progressed to severe pleural and peribronchovascular fibrosis, reminiscent of changes observed in restrictive allograft syndrome. Lung transplantation into splenectomized B6 alymphoplastic (aly/aly) or splenectomized B6 lymphotoxin-β receptor-deficient mice demonstrated that recipient secondary lymphoid organs, such as spleen and lymph nodes, are necessary for progression from acute cellular rejection to allograft fibrosis in this model. Our work uncovered a critical role for recipient secondary lymphoid organs in the development of CLAD after pulmonary transplantation and may provide mechanistic insights into the pathogenesis of this complication.

摘要

慢性肺移植功能障碍（CLAD）仍然是肺移植后长期生存的主要限制因素之一。我们修改了 CLAD 的小鼠模型，并将 BALB/c 供体的左肺移植到术后接受间歇性环孢素和甲基强的松龙治疗的 B6 受体中。在该模型中，肺移植物在第 15 天发生急性细胞排斥反应，在移植后第 30 天进展为严重的胸膜和支气管血管周围纤维化，类似于在限制型移植物综合征中观察到的变化。将肺移植到脾切除的 B6 无淋巴形成（aly/aly）或脾切除的 B6 淋巴毒素-β 受体缺陷型小鼠中表明，受体二级淋巴器官，如脾和淋巴结，对于该模型中从急性细胞排斥反应进展为移植物纤维化是必需的。我们的工作揭示了受体二级淋巴器官在肺移植后 CLAD 发展中的关键作用，并可能为该并发症的发病机制提供机制见解。