Neutrophil depletion attenuates antibody-mediated rejection in a renal transplantation mouse model

作者全名："Li, Xingku; Zhao, Yakun; Sun, Wenying; Zhang, Cong; Yu, Yadi; Du, Bo; Jin, AiShun; Liu, Ye"

作者地址："[Li, Xingku; Du, Bo] Harbin Med Univ, Affiliated Hosp 2, Expt Res Ctr, Harbin, Peoples R China; [Zhao, Yakun] Harbin Med Univ, Affiliated Hosp 2, Dept Urol, Harbin, Peoples R China; [Sun, Wenying] Harbin Med Univ, Affiliated Hosp 2, Clin Lab, Harbin, Peoples R China; [Zhang, Cong] Heilongjiang Univ Chinese Med, Coll Basic Med, Dept Microbiol & Immunol, Harbin, Peoples R China; [Yu, Yadi; Jin, AiShun; Liu, Ye] Harbin Med Univ, Coll Basic Med, Dept Immunol, Harbin 150086, Peoples R China; [Jin, AiShun] Chongqing Med Univ, Coll Basic Med, Dept Immunol, Chongqing, Peoples R China"

通信作者："Jin, AS; Liu, Y (通讯作者)，Harbin Med Univ, Coll Basic Med, Dept Immunol, Harbin 150086, Peoples R China."

来源：CLINICAL AND EXPERIMENTAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001136254400001

JCR分区：Q3

影响因子：3.4

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：antibody-mediated rejection; kidney transplantation; neutrophil; BAFF; APRIL

摘要："Antibody-mediated rejection (AMR) can cause graft failure following renal transplantation. Neutrophils play a key role in AMR progression, but the exact mechanism remains unclear. We investigated the effect of neutrophils on AMR in a mouse kidney transplantation model. The mice were divided into five groups: syngeneic transplantation (Syn), allograft transplantation (Allo), and three differently treated AMR groups. The AMR mouse model was established using skin grafts to pre-sensitize recipient mice. Based on the AMR model, Ly6G-specific monoclonal antibodies were administered to deplete neutrophils (NEUT-/- + AMR) and TACI-Fc was used to block B-cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) signaling (TACI-Fc + AMR). Pathological changes were assessed using hematoxylin-eosin and immunohistochemical staining. Banff values were evaluated using the Banff 2015 criteria. Donor-specific antibody (DSA) levels were assessed using flow cytometry, and BAFF and APRIL concentrations were measured using ELISA. Compared to the Syn and Allo groups, a significantly increased number of neutrophils and increased C4d and IgG deposition were observed in AMR mice, accompanied by elevated DSA levels. Neutrophil depletion inhibited inflammatory cell infiltration and reduced C4d and IgG deposition. Neutrophil depletion significantly decreased DSA levels after transplantation and suppressed BAFF and APRIL concentrations, suggesting a mechanism for attenuating AMR-induced graft damage. Similar results were obtained after blockading BAFF/APRIL using a TACI-Fc fusion protein. In summary, neutrophil infiltration increased in the AMR mouse renal transplantation model. Neutrophil depletion or blockading the BAFF/APRIL signaling pathway significantly alleviated AMR and may provide better options for the clinical treatment of AMR. We established the AMR mouse model and significantly increased neutrophil infiltration was only observed in the kidney tissues of the AMR mice. Neutrophil depletion might reduce rejection in AMR mice by causing a decrease in BAFF and APRIL levels. The TACI-Fc fusion protein alleviated kidney injury after transplantation in AMR mice by reducing BAFF and APRIL concentrations. Graphical Abstract"

基金机构：Heilongjiang Academy of Medical Sciences [201802]

基金资助正文："The supply of equipment, and materials in the authors' group is supported by the Heilongjiang Academy of Medical Sciences under grant agreement No. 201802 (Study on the correlation between donor-specific antibody and complement C1q in renal transplantation rejection)."