361.4: Mitigating alloimmune rejection using Circular RNA AEBP2-silenced DC in heart transplantation: A new target for tolerogenic DCs.

作者：Qingfeng Zhou, Amal Abuomar, Raj Kumar Thapa, Serina Chahal, Tan Ze Wang, Adam Greasley, Xiufen Zheng · 发表于：Transplantation · 年份：2024 · DOI：10.1097/01.tp.0001065864.56829.1c · 研究领域：Circular RNAs in diseases、Viral Infections and Immunology Research、Transplantation: Methods and Outcomes

Introduction: Circular RNA (circRNA), a new type of single -stranded RNAs generated by back-splicing, plays vital roles in cellular activities. However, the impact of circRNAs on dendritic cell (DCs)-mediated immune modulation and allo immune rejection is not well investigated. Our microarray assays show that circRNA is differentially expresed in DCs. One of circRNA known as circAENP which is backspliced from the AEBP2 gene is highly expressed in mature immune reactive DCs. We hypothesize that silencing of circAEBP2 in DC will induce immunosuppressive DCs which can prevent allograft rejection after heart transplantation Methods: Bone marrow- derived DCs were cultured in vitro. Day 5 of cultured DCs were transfected with siRNA specifically targeting circAEBP2 for 48 h. DC phenotyping was conducted by measuring the expression of CD11c, MHCII, and costimulatory molecules (CD40 and CD80) by flow cytometry. MLRs were conducted to measure DCs’ function to activate allogeneic naïve T cells and to generate regulatory T cells (Treg) in vitro. CircAEBP2 silenced DCs were administrated to recipient mice seven days prior to MHC-full mismated mouse heart transplantation. Allograft survival was observed to assess the impact of circAEBP2 silenced immunosuppressive DCs on alloimmune rejection in organ transplantation. Histopathological changes of transplanted hearts were assessed Results: Knockdown of circAEBP2 reduced the expression of costimulatory molecules (CD 40 and CD80) and proinflamm...