Song Jiangping, Su Wenjun, Chen Xiao, Zhao Qian, Zhang Ningning, Li Mao-Gang, Yang Ping-Chang, Wang Liqing
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Xicheng District, Beijing, 100037, China.
The Research Center of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China.
Oncotarget. 2017 Apr 25;8(17):28237-28246. doi: 10.18632/oncotarget.16000.
The immune tolerance to the transplant heart survival is critical. Regulatory B cells are one of the major immune regulatory cell populations in the immune tolerance. Micro RNAs (miR) can regulate the activities of immune cells, such as the expression of interleukin (IL)-10 by B cells. This study tests a hypothesis that micro RNA (miR)-98 plays a role in the regulation of interleukin (IL)-10 expression in B cells (B10 cell) after heart transplantation. In this study, the peripheral blood samples were collected from patients before and after heart transplantation. The expression of miR-98 and IL-10 in B cells was assessed by real time RT-PCR. An allograft heart transplantation mouse model was developed. We observed that after heart transplantation, the frequency of peripheral B10 cell and the IL-10 mRNA levels in peripheral B cells were significantly decreased, the levels of miR-98 were increased in peripheral B cells and the serum levels of cortisol were increased in the patients. Treating naive B cells with cortisol in the culture suppressed the expression of IL-10 in B cells, which was abolished by knocking down the miR-98 gene. Administration with anti-miR-98, or cortisol inhibitor, or adoptive transfer with B10 cells, significantly enhanced the survival rate and time of mice received allograft heart transplantation. In conclusion, the enhancement of serum cortisol affects the immune tolerant feature of B cells, which can be attenuated by anti-miR-98-carrying liposomes.
对移植心脏存活的免疫耐受至关重要。调节性B细胞是免疫耐受中主要的免疫调节细胞群体之一。微小RNA(miR)可调节免疫细胞的活性,如B细胞中白细胞介素(IL)-10的表达。本研究检验了一个假设,即微小RNA(miR)-98在心脏移植后B细胞(B10细胞)白细胞介素(IL)-10表达的调节中发挥作用。在本研究中,收集了心脏移植患者术前和术后的外周血样本。通过实时RT-PCR评估B细胞中miR-98和IL-10的表达。建立了同种异体心脏移植小鼠模型。我们观察到,心脏移植后,外周B10细胞频率和外周B细胞中IL-10 mRNA水平显著降低,外周B细胞中miR-98水平升高,患者血清皮质醇水平升高。在培养中用皮质醇处理幼稚B细胞可抑制B细胞中IL-10的表达,敲低miR-98基因可消除这种抑制作用。给予抗miR-98、皮质醇抑制剂或进行B10细胞过继转移,可显著提高接受同种异体心脏移植小鼠的存活率和存活时间。总之,血清皮质醇水平升高影响B细胞的免疫耐受特性,携带抗miR-98的脂质体可减弱这种影响。