| Li Xin,Zhao Ke,Sun Huiying,Ren Guangming,Gao Huiying,Li Changyan,Ning Hongmei.Knockout of BRCC3 aggravates acute GVHD in allogeneic hematopoietic stem cell transplant recipient mice[J].Chinese Journal of Radiological Medicine and Protection,2022,42(6):401-407 |
| Knockout of BRCC3 aggravates acute GVHD in allogeneic hematopoietic stem cell transplant recipient mice |
| Received:March 03, 2022 |
| DOI：10.3760/cma.j.cn112271-20220303-00077 |
| KeyWords:BRCC3 aGVHD T cell activation Therapy target |
| FundProject:蛋白质组学国家重点实验室开放课题(SKLP-O201804) |
| Author Name | Affiliation | E-mail | | Li Xin | Department of Hematology, Fifth Medical Center of PLA General Hospital, Fifth School of Clinical Medicine, Anhui Medical University, Hefei 230032, China | | | Zhao Ke | Beijing Institute of Lifeomics, Academy of Military Sciences, Beijing 100850, China | | | Sun Huiying | Beijing Institute of Lifeomics, Academy of Military Sciences, Beijing 100850, China | | | Ren Guangming | Beijing Institute of Lifeomics, Academy of Military Sciences, Beijing 100850, China | | | Gao Huiying | Beijing Institute of Lifeomics, Academy of Military Sciences, Beijing 100850, China | | | Li Changyan | Beijing Institute of Lifeomics, Academy of Military Sciences, Beijing 100850, China | | | Ning Hongmei | Department of Hematology, Fifth Medical Center of PLA General Hospital, Fifth School of Clinical Medicine, Anhui Medical University, Hefei 230032, China | ninghongmei72@sina.com |
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| 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, 1×107 bone marrow cells and 8×106 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. |
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