title: Thymic stromal lymphopoietin attenuates the development of atherosclerosis in ApoE-/- mice.
abstract: BACKGROUND
  Thymic stromal lymphopoietin (TSLP) is a cytokine with multiple effects on the body. For one thing, TSLP induces Th2 immunoreaction and facilitates allergic reaction; for another, it promotes the differentiation of naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) and maintains immune tolerance. However, the exact role of TSLP in atherosclerosis remains unknown.
  
  
  RESULTS
  In vitro, we examined the phenotype of TSLP-conditioned bone marrow dendritic cells (TSLP-DCs) of apolipoprotein E-deficient (ApoE-/-) mice and their capacity to induce the differentiation of Tregs. Our results indicated that TSLP-DCs obtained the characteristics of tolerogenic dendritic cells and increased a generation of CD4+ latency-associated peptide (LAP)+ Tregs and nTregs when cocultured with naive T cells. In addition, the functional relevance of TSLP and TSLP-DCs in the development of atherosclerosis was also determined. Interestingly, we found that TSLP was almost absent in cardiovascular tissue of ApoE-/- mice, and TSLP administration increased the levels of antioxidized low-density lipoprotein IgM and IgG1, but decreased the levels of IgG2a in plasma. Furthermore, mice treated with TSLP and TSLP-DCs developed significantly fewer (32.6% and 28.2%, respectively) atherosclerotic plaques in the aortic root compared with controls, along with increased numbers of CD4+LAP+ Tregs and nTregs in the spleen and decreased inflammation in the aorta, which could be abrogated by anti-TGF-β antibody.
  
  
  CONCLUSIONS
  Our results revealed a protective role for TSLP in atherosclerosis that is possibly mediated by reestablishing a tolerogenic immune response, which may represent a novel possibility for treatment or prevention of atherosclerosis.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Kunwu
authors.initials: K
authors.lastname: Yu
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhu
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Zhong
authors.forename: Zhengfeng
authors.initials: Z
authors.lastname: Zhu
authors.forename: Yingzhong
authors.initials: Y
authors.lastname: Lin
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Kai
authors.initials: K
authors.lastname: Meng
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Ji
authors.forename: Guiwen
authors.initials: G
authors.lastname: Yi
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Bangwei
authors.initials: B
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Mao
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Mao
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000517:prevention & control; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D016212:Transforming Growth Factor beta; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
keywords: CD4+LAP+ Tregs; TGF‐β; TSLP; atherosclerosis; tolerogenic dendritic cells