Chun Wu1, Shaolin He2, Yudong Peng3, Kishan Kumar Kushwaha4, Jing Lin5, Jiangchuan Dong6, Boyuan Wang7, Jibin Lin8, Shengshuai Shan9, Jing Liu10, Kai Huang11, Dazhu Li12. 1. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: wlky707@126.com. 2. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 17772979@qq.com. 3. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: am-penicillin@163.com. 4. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: kishan@163.com. 5. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 767130054@qq.com. 6. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 337417207@qq.com. 7. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 188237154@qq.com. 8. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 136052857@qq.com. 9. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 451841811@qq.com. 10. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 459823429@qq.com. 11. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: huangkail@yahoo.com. 12. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: lidazhuhp@sohu.com.
Abstract
AIMS: We generated thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice to directly explore the role of thymic stromal lymphopoietin (TSLP) in atherogenesis. METHODS AND RESULTS: Both thymic stromal lymphopoietin (TSLP) and its receptor are expressed in atherosclerotic aortas of apolipoprotein E knockout (ApoE KO) mice. Serum thymic stromal lymphopoietin (TSLP) is markedly increased in apolipoprotein E knockout (ApoE KO) mice fed with a high fat diet (HFD). Arterial lesion formation was significantly decreased in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice compared with apolipoprotein E knockout (ApoE KO) mice. Bone marrow chimera studies indicated reduced lesions in apolipoprotein E knockout (ApoE KO) mice which received the bone marrow of thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice as well as in TSLPR KO mice which received bone marrow of ApoE-TSLPR DKO mice. Compared with apolipoprotein E knockout (ApoE KO) mice, IFN-γ secretion by activated T cells was increased but IL-4 expression was reduced in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice. Consisted with these results, the mRNA of IFN-γ was increased but IL-4 was reduced in root. These findings suggest that a reduction in atherosclerotic lesions in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice may not be due to a Th1/Th2 imbalance. On the other hand, the number of Th17 cells, the secretion of IL-17A by activated CD4(+) T cells and the mRNA expression of IL-17A in root were decreased in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice. Notably, the number of regulatory T cell expression of IL-10 was increased in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice. CONCLUSIONS: Collectively, our data suggest that activating thymic stromal lymphopoietin (TSLP) promotes atherosclerosis by inducing Th17/Treg imbalance through thymic stromal lymphopoietin/thymic stromal lymphopoietin R-receptor (TSLP/TSLPR) signal way in apolipoprotein E-deficient mice fed with HFD model.
AIMS: We generated thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice to directly explore the role of thymic stromal lymphopoietin (TSLP) in atherogenesis. METHODS AND RESULTS: Both thymic stromal lymphopoietin (TSLP) and its receptor are expressed in atherosclerotic aortas of apolipoprotein E knockout (ApoE KO) mice. Serum thymic stromal lymphopoietin (TSLP) is markedly increased in apolipoprotein E knockout (ApoE KO) mice fed with a high fat diet (HFD). Arterial lesion formation was significantly decreased in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice compared with apolipoprotein E knockout (ApoE KO) mice. Bone marrow chimera studies indicated reduced lesions in apolipoprotein E knockout (ApoE KO) mice which received the bone marrow of thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice as well as in TSLPR KO mice which received bone marrow of ApoE-TSLPR DKO mice. Compared with apolipoprotein E knockout (ApoE KO) mice, IFN-γ secretion by activated T cells was increased but IL-4 expression was reduced in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice. Consisted with these results, the mRNA of IFN-γ was increased but IL-4 was reduced in root. These findings suggest that a reduction in atherosclerotic lesions in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice may not be due to a Th1/Th2 imbalance. On the other hand, the number of Th17 cells, the secretion of IL-17A by activated CD4(+) T cells and the mRNA expression of IL-17A in root were decreased in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice. Notably, the number of regulatory T cell expression of IL-10 was increased in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice. CONCLUSIONS: Collectively, our data suggest that activating thymic stromal lymphopoietin (TSLP) promotes atherosclerosis by inducing Th17/Treg imbalance through thymic stromal lymphopoietin/thymic stromal lymphopoietin R-receptor (TSLP/TSLPR) signal way in apolipoprotein E-deficient mice fed with HFD model.
Authors: Maaz B J Syed; Alexander J Fletcher; Marc R Dweck; Rachael Forsythe; David E Newby Journal: Trends Cardiovasc Med Date: 2018-12-27 Impact factor: 6.677
Authors: Martin Steinmetz; Ludivine Laurans; Sarah Nordsiek; Lena Weiß; Bieke van der Veken; Padmapriya Ponnuswamy; Bruno Esposito; Marie Vandestienne; Andreas Giraud; Cristina Göbbel; Eva Steffen; Tobias Radecke; Stephane Potteaux; Georg Nickenig; Tienush Rassaf; Alain Tedgui; Ziad Mallat Journal: J Cell Mol Med Date: 2020-04-13 Impact factor: 5.310