Extracellular Vesicles Mediate Immune Responses to Tissue-Associated Self-Antigens: Role in Solid Organ Transplantations.
Extracellular Vesicles Mediate Immune Responses to Tissue-Associated Self-Antigens: Role in Solid Organ Transplantations.
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DOI：
10.3389/fimmu.2022.861583
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
移植是诊断为终末期器官疾病的患者的治疗选择;然而，移植器官的免疫和非免疫反应排斥反应影响移植物的长期存活。几项研究表明，肾、心脏和肺移植后可发生急性和慢性排斥反应。供体特异性抗体（HLA-DSA）的从头合成与急性和慢性排斥反应的发生之间有很强的相关性;然而，一些慢性排斥反应的移植受者没有可检测到的HLA-DSA。对这些患者血清的研究表明，对组织相关抗原（TaAg）的免疫应答也可能在慢性排斥反应的发生中起重要作用，无论是单独还是与HLA-DSA联合。HLA-DSAs和TaAgs抗体之间的协同效应正在建立，但潜在的机制尚未确定。我们假设HLA-DSA损伤移植的供体器官，导致应激并导致细胞外囊泡的释放，这有助于慢性排斥反应。这些囊泡表达供体人白细胞抗原（HLA）和非HLA TaAg两者，其可以激活抗原呈递细胞并导致免疫应答和针对供体HLA和非HLA组织相关Ag两者的抗体的产生。由于生理和病理条件，细胞在许多情况下释放胞外囊泡（EV）。我们的研究小组首先采用从经历急性或慢性排斥反应的人肺移植受者获得的临床标本，证明循环细胞外囊泡显示不匹配的供体HLA分子和肺相关Ag（胶原-V和K-α 1微管蛋白）。本文综述了近年来组织相关抗原抗体在器官移植排斥反应，特别是慢性排斥反应中的重要作用。我们还将讨论从移植器官中释放的细胞外囊泡在实体器官移植后同种免疫和自身免疫对组织相关抗原之间的相互作用中的重要作用。
Transplantation is a treatment option for patients diagnosed with end-stage organ diseases; however, long-term graft survival is affected by rejection of the transplanted organ by immune and nonimmune responses. Several studies have demonstrated that both acute and chronic rejection can occur after transplantation of kidney, heart, and lungs. A strong correlation has been reported between de novo synthesis of donor-specific antibodies (HLA-DSAs) and development of both acute and chronic rejection; however, some transplant recipients with chronic rejection do not have detectable HLA-DSAs. Studies of sera from such patients demonstrate that immune responses to tissue-associated antigens (TaAgs) may also play an important role in the development of chronic rejection, either alone or in combination with HLA-DSAs. The synergistic effect between HLA-DSAs and antibodies to TaAgs is being established, but the underlying mechanism is yet to be defined. We hypothesize that HLA-DSAs damage the transplanted donor organ resulting in stress and leading to the release of extracellular vesicles, which contribute to chronic rejection. These vesicles express both donor human leukocyte antigen (HLA) and non-HLA TaAgs, which can activate antigen-presenting cells and lead to immune responses and development of antibodies to both donor HLA and non-HLA tissue-associated Ags. Extracellular vesicles (EVs) are released by cells under many circumstances due to both physiological and pathological conditions. Primarily employing clinical specimens obtained from human lung transplant recipients undergoing acute or chronic rejection, our group has demonstrated that circulating extracellular vesicles display both mismatched donor HLA molecules and lung-associated Ags (collagen-V and K-alpha 1 tubulin). This review focuses on recent studies demonstrating an important role of antibodies to tissue-associated Ags in the rejection of transplanted organs, particularly chronic rejection. We will also discuss the important role of extracellular vesicles released from transplanted organs in cross-talk between alloimmunity and autoimmunity to tissue-associated Ags after solid organ transplantation.
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影响因子：
13.6
作者：
Antonioli L;Pacher P;Vizi ES;Haskó G
通讯作者：
Haskó G
影响因子：
7.3
作者：
Agarwal A;Fanelli G;Letizia M;Tung SL;Boardman D;Lechler R;Lombardi G;Smyth LA
通讯作者：
Smyth LA
影响因子：
4.6
作者：
Aiello S;Rocchetta F;Longaretti L;Faravelli S;Todeschini M;Cassis L;Pezzuto F;Tomasoni S;Azzollini N;Mister M;Mele C;Conti S;Breno M;Remuzzi G;Noris M;Benigni A
通讯作者：
Benigni A
影响因子：
15.9
作者：
Burlingham, William J.;Love, Robert B.;Willkes, David S.
通讯作者：
Willkes, David S.
影响因子：
24.3
作者：
Admyre, C;Grunewald, J;Gabrielsson, S
通讯作者：
Gabrielsson, S