Date: Monday, June 3, 2019
Session Time: 2:30pm-4:00pm
Presentation Time: 3:18pm-3:30pm
Location: Room 311
*Purpose: The expression of the Aire (Autoimmune regulator) gene was observed to inhibit the maturation and activation of dendritic cells (DCs) and induce transplantation tolerance.
*Methods: The bone marrow-derived DCs were cultured in vitro, and the Aire gene was transferred into DCs by means of green fluorescent protein (GFP) fluorescent adenoviral vector. The Aire gene-modified immature (imDCs) was detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA). The phenotypic and functional changes of DCs before and after lipopolysaccharide (LPS) stimulation were established. A mouse model of abdominal heterotopic heart transplantation was established. Three days after the operation, the receptors were administered to the dorsal vein of the penis for injection of phosphate buffered saline (PBS) and imDCs. DC-GFP and DC-Aire were used to observe the heart graft activity and survival time of each group of mice. At the same time, the grafts were taken for hematoxylin-eosin (HE) and immunofluorescence on the 11th and 100th day after operation. The graft rejection intensity of each group was compared.
*Results: DCs overexpressing Aire remained stable in immature state after lipopolysaccharide stimulation: low expression of human major histocompatibility complex (MHC)-II, CD40, CD80, CD86, secretion of low-level interleukin (IL)-12 [(536.80±93.46) pg/ml, p=0.014] and high level IL-10 [(420.50±38.69) pg/ml, P=0.024], and the difference between the two groups was statistically significant. Postoperative graft survival time in the Aire group was significantly better than the other groups [(28.6 ± 4.8) d, P = 0.016]. Postoperative immunohistochemistry suggested that the heart graft activity in the Aire group was superior to other controls.
*Conclusions: Aire gene effectively inhibited the maturation and activation of immature DCs under the action of exogenous stimulating factors such as lipopolysaccharide, inhibiting antigen presentation, prolonging graft survival to some extent, and inducing transplantation of immune tolerance.
To cite this abstract in AMA style:Zhang Y, Zhu Z, Chen M, Huang S, Sun C, Ju W, Guo Z, He X. Dendritic Cells Transduced with Autoimmune Regulator Exhibit Immature Properties and Prolong Heart Allograft Survival [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/dendritic-cells-transduced-with-autoimmune-regulator-exhibit-immature-properties-and-prolong-heart-allograft-survival/. Accessed May 9, 2021.
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