Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.
Front Immunol. 2021 May 12;12:682749. doi: 10.3389/fimmu.2021.682749. eCollection 2021.
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-B 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-B signaling to suppress B cell immune responses, thereby decreasing the DSA level.
抗体介导的排斥反应 (AMR) 是实体器官移植中外来移植物功能障碍的主要原因，并导致移植物衰竭。环状螺旋 B 肽 (CHBP) 是一种新型的促红细胞生成素衍生肽，可改善肾移植模型中的肾移植排斥反应。然而，其对 AMR 的影响尚不清楚。本研究旨在通过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 小鼠的皮肤移植到接受或未接受 CHBP 治疗的 C57BL/6 小鼠中创建。还创建了二次同基因皮肤移植模型，涉及从 C57BL/6 小鼠到 C57BL/6 小鼠的移植，作为对照。分析皮肤移植物排斥、皮肤移植物中 CD19 B 细胞浸润、脾浆细胞、生发中心 (GC) B 细胞和 Tfh 细胞的百分比、供体特异性抗体 (DSA) 的血清水平以及脾细胞中的 NF-B 信号转导。与同种异体组相比，CHBP 组的皮肤移植物存活时间明显延长。CHBP 治疗还显著减少了皮肤移植物中的 CD19 B 细胞浸润，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 下调了脾细胞中的 P100、RelB 和 P52。CHBP 通过抑制 AMR 延长皮肤移植物存活时间，这可能是通过抑制 NF-B 信号转导抑制 B 细胞免疫反应来实现的，从而降低 DSA 水平。
