Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model.

Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model.
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环状螺旋 B 肽通过抑制小鼠模型中的 B 细胞免疫反应来延长同种异体皮肤移植物的存活率

DOI:
10.3389/fimmu.2021.682749
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发表时间:
2021
影响因子:
7.3
通讯作者:
Zhu D
Zhu D
中科院分区:
医学2区
文献类型:
--
作者:
Zheng L;Wang X;Hu L;Gao W;Zhang W;Zhang X;Hu C;Rong R;Yang C;Zhu D

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抗体介导的排斥反应(Antibody-mediated rejection,AMR)是实体器官移植中同种异体移植物功能障碍的主要原因,并导致同种异体移植物衰竭。环螺旋B肽(CHBP)是一种新的促红细胞生成素衍生肽,在肾移植模型中可改善肾移植排斥反应。然而,其对抗生素耐药性的影响仍然未知。本研究旨在使用二次同种异体皮肤移植模型研究CHBP对AMR的影响,该模型通过将BALB/c小鼠的皮肤移植到C57 BL/6小鼠,使用或不使用CHBP处理来创建。还建立了包括从C57 BL/6小鼠移植到C57 BL/6小鼠的二次同基因皮肤移植模型作为对照。观察移植皮片排斥反应、移植皮片中CD 19 + B细胞浸润、脾浆细胞、生发中心(GC)B细胞和Tfh细胞百分比、血清供体特异性抗体(DSA)水平和脾细胞NF-κB信号。与同种异体移植组相比,CHBP组的皮肤移植物存活时间显著延长。CHBP治疗还显著减少了移植皮肤中CD 19 + B细胞的浸润,降低了脾浆细胞、GC B细胞和Tfh细胞的百分比,并改善了血清DSA水平的升高。在分子水平上,CHBP下调脾细胞中的P100、RelB和P52。CHBP通过抑制AMR延长移植皮肤存活,其机制可能是通过抑制NF-κB信号通路抑制B细胞免疫反应,从而降低DSA水平。
Antibody-mediated rejection (AMR) represents a major cause of allograft dysfunction and results in allograft failure in solid organ transplantation. Cyclic helix B peptide (CHBP) is a novel erythropoietin-derived peptide that ameliorated renal allograft rejection in a renal transplantation model. However, its effect on AMR remains unknown. This study aimed to investigate the effect of CHBP on AMR using a secondary allogeneic skin transplantation model, which was created by transplanting skin from BALB/c mice to C57BL/6 mice with or without CHBP treatment. A secondary syngeneic skin transplantation model, involving transplantation from C57BL/6 mice to C57BL/6 mice, was also created to act as a control. Skin graft rejection, CD19+ B cell infiltration in the skin allograft, the percentages of splenic plasma cells, germinal center (GC) B cells, and Tfh cells, the serum levels of donor specific antibodies (DSAs), and NF-κB signaling in splenocytes were analyzed. Skin allograft survival was significantly prolonged in the CHBP group compared to the allogeneic group. CHBP treatment also significantly reduced the CD19+ B cell infiltration in the skin allograft, decreased the percentages of splenic plasma cells, GC B cells, and Tfh cells, and ameliorated the increase in the serum DSA level. At a molecular level, CHBP downregulated P100, RelB, and P52 in splenocytes. CHBP prolonged skin allograft survival by inhibiting AMR, which may be mediated by inhibition of NF-κB signaling to suppress B cell immune responses, thereby decreasing the DSA level.
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