Xiaoguang Xu1, Haiyan Huang1, Qiang Wang1, Ming Cai1, Yeyong Qian1, Yong Han1, Xinying Wang1, Yu Gao1, Ming Yuan1, Liang Xu1, Chen Yao1, Li Xiao2, Bingyi Shi3. 1. Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China. 2. Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China. Electronic address: xiaolilab309@163.com. 3. Organ Transplantation Institute, The 309th Hospital of Chinese People's Liberation Army and Beijing Key Laboratory of Organ Transplant and Immune Regulation, 17th Heishanhu Road, Haidian District, Beijing 100091, China. Electronic address: shibingyi@medmail.com.cn.
Abstract
PURPOSE: IFN-γ is a protypical proinflammatory cytokine that plays a central role in inflammation and acute graft rejection. Accumulating evidence indicates that IFN-γ can exert previously unexpected immunoregulatory activities. However, little is known about the role of IFN-γ secreted by Th1-like regulatory T cells in human kidney transplantation. METHODS: To determine the function of IFN-γ in acute T cell-mediated renal allograft rejection (ACR), we examined serum cytokine expression profiles in ACR patients by human cytokine multiplex immunoassay and analyzed the cellular origins of IFN-γ in peripheral blood and renal allograft biopsies from ACR cases and controls by flow cytometry and immunohistochemistry, respectively. RESULTS: The results showed significant reduction in serum concentrations of Th1-inducing cytokines IL-12p70 and IFN-γ as well as Th2-related cytokine IL-4 in ACR patients compared with stable controls. However, levels of several Th1-, Th2- and Th17-related cytokines, such as IL-2, TNF-α, TNF-β, IL-12 (p40), IL-10, IL-15, IL-17, IL-21, and IL-23, as well as the frequencies of Th1 and Th17 cell, did not differ between ACR cases and stable controls. Moreover, we found the levels of IFN-γ were correlated with those of the anti-inflammatory factor, IL-1 receptor antagonist (IL-1Ra) in ACR. Notably, the Th1-like Treg cell-to-Foxp3- Th1 cell ratio was significantly lower in ACR patients compared with that in stable controls. In graft biopsies from ACR patients, Treg cells and Th1-like Treg cells were less abundant than those without ACR. CONCLUSIONS: Our study indicates that IFN-γ secreted from Th1-like Treg cells negatively modulates ACR.
PURPOSE: IFN-γ is a protypical proinflammatory cytokine that plays a central role in inflammation and acute graft rejection. Accumulating evidence indicates that IFN-γ can exert previously unexpected immunoregulatory activities. However, little is known about the role of IFN-γ secreted by Th1-like regulatory T cells in human kidney transplantation. METHODS: To determine the function of IFN-γ in acute T cell-mediated renal allograft rejection (ACR), we examined serum cytokine expression profiles in ACRpatients by human cytokine multiplex immunoassay and analyzed the cellular origins of IFN-γ in peripheral blood and renal allograft biopsies from ACR cases and controls by flow cytometry and immunohistochemistry, respectively. RESULTS: The results showed significant reduction in serum concentrations of Th1-inducing cytokines IL-12p70 and IFN-γ as well as Th2-related cytokine IL-4 in ACRpatients compared with stable controls. However, levels of several Th1-, Th2- and Th17-related cytokines, such as IL-2, TNF-α, TNF-β, IL-12 (p40), IL-10, IL-15, IL-17, IL-21, and IL-23, as well as the frequencies of Th1 and Th17 cell, did not differ between ACR cases and stable controls. Moreover, we found the levels of IFN-γ were correlated with those of the anti-inflammatory factor, IL-1 receptor antagonist (IL-1Ra) in ACR. Notably, the Th1-like Treg cell-to-Foxp3- Th1 cell ratio was significantly lower in ACRpatients compared with that in stable controls. In graft biopsies from ACRpatients, Treg cells and Th1-like Treg cells were less abundant than those without ACR. CONCLUSIONS: Our study indicates that IFN-γ secreted from Th1-like Treg cells negatively modulates ACR.
Authors: Yin Zongyi; Zou Funian; Li Hao; Wang Xin; Cheng Ying; Zhang Jialin; Liu Yongfeng; Li Baifeng Journal: PLoS One Date: 2017-12-13 Impact factor: 3.240