title: TSLPR deficiency attenuates atherosclerotic lesion development associated with the inhibition of TH17 cells and the promotion of regulator T cells in ApoE-deficient mice.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: wlky707@126.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 17772979@qq.com.
authors.forename: Shaolin
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: am-penicillin@163.com.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: kishan@163.com.
authors.forename: Kishan Kumar
authors.initials: KK
authors.lastname: Kushwaha
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 767130054@qq.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 337417207@qq.com.
authors.forename: Jiangchuan
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 188237154@qq.com.
authors.forename: Boyuan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 136052857@qq.com.
authors.forename: Jibin
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 451841811@qq.com.
authors.forename: Shengshuai
authors.initials: S
authors.lastname: Shan
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 459823429@qq.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: huangkail@yahoo.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: lidazhuhp@sohu.com.
authors.forename: Dazhu
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D007136:Immunoglobulins / Q000235:genetics* / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018121:Receptors, Cytokine / Q000235:genetics* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D007136:Immunoglobulins; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse
keywords: Atherosclerosis; Th17 cells; Thymic stromal lymphopoietin; Treg cells