Knockout of BRCC3 aggravates acute GVHD in allogeneic hematopoietic stem cell transplant recipient mice
10.3760/cma.j.cn112271-20220303-00077
- VernacularTitle:敲除BRCC3加重异基因造血干细胞移植受体小鼠急性移植物抗宿主病
- Author:
Xin LI
1
;
Ke ZHAO
;
Huiying SUN
;
Guangming REN
;
Huiying GAO
;
Changyan LI
;
Hongmei NING
Author Information
1. 安徽医科大学解放军总医院第五医学临床学院血液科，合肥 230032
- Keywords:
BRCC3;
aGVHD;
T cell activation;
Therapy target
- From:
Chinese Journal of Radiological Medicine and Protection
2022;42(6):401-407
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect and underlying mechanism of BRCC3 knockout on acute GVHD(aGVHD) of mice.Methods:A total of 12 recipient C57BL/6J mice were divided into two groups, including 6 wild type(WT) and BRCC3 -/-(KO). The recipients were exposed to 4.5 Gy + 4.5 Gy 60Co γ-rays in total body irradiation (TBI) at 30 min intervals. At 6 h post-irradiation, 1×10 7bone marrow cells and 8×10 6 splenocytes from BALB/c mice were infused into C57BL/6J mouse via tail vein to develop aGVHD mouse model. BRCC3 was specifically knocked out in aGVHD mouse model. The organ damage was examined through histopathology. The levels of serum cytokines were measured by enzyme-linked immuno sorbent assay (ELISA) and cytometric bead array (CBA), respectively. Spleen, liver and small intestine lymphocytes were isolated at 9 d post-transplantation, and the infiltration and activation of T cells in the target organs were assayed using flow cytometry. Results:The absence of BRCC3 in recipient mice significantly shortened survival ( P<0.05) with increased liver injury of aGVHD mice. In BRCC3 -/-recipient mice, the proportions of CD8+ T cells and CD8+ CD25+ T cells were significantly higher than those in the spleen( t=6.53, 5.52, P<0.05), and the proportions of CD8+ T cells and CD8+ CD25+ T cells were significantly increased in the liver ( t=3.74, 3.19, P<0.05). Similarly, the proportions of CD8+ T cells, CD8+ CD25+ T cells and CD8+ CD69+ T cells were significantly elevated in the small intestine ( t=3.52, 4.06, 3.29, P<0.05). Conclusions:BRCC3 deletion increased the proliferation and activation of donor CD8+ T cells and aggravated aGVHD, which might provide a new prevention and treatment target for aGVHD.
