Disruption of the TSLP-TSLPR-LAP signaling between epithelial and dendritic cells through hyperlipidemia contributes to regulatory T-Cell defects in atherosclerotic mice
Regulatory T-Cells (Tregs) play a protective role against the development of atherosclerosis. Moreover, thymic stromal lymphopoietin (TSLP)/thymic stromal lymphopoietin receptor (TSLPR) signaling in myeloid dendritic cells (DCs) promote Treg differentiation. Here, we examined the potential role of TSLP/TSLPR on Treg homeostasis in atherosclerosis. The frequencies of both latency-associated peptide (LAP)(+) and Foxp3(+) Tregs were reduced in the thymus and spleen of ApoE(-/-) mice compared with C57BL/6 mice, and this effect was associated with decreased thymic output. The tolerogenic function of DCs obtained from ApoE(-/-) mice was compromised compared with those from C57BL/6 mice. The expression of TSLP and TSLPR was also inhibited in ApoE(-/-) mice. In addition, we found that ox-LDL attenuated TSLP expression in cultured thymic epithelial cells (TECs) through the activation of retinoid X receptor alpha (RXRA) and IL-1 beta and decreased LAP and PD-L1 expression in oxLDL-activated DCs while both were up-regulated in TSLP-activated DCs. We also observed that the TSLP-DCs mediated differentiation of Tregs was abrogated through LAP neutralization. Furthermore, TSLP injection rescued Treg defects in ApoE(-/-) mice. These findings suggest that Treg defects in ApoE(-/-) mice might partially be attributed to the disruption of TSLP-TSLPR-LAP signaling in epithelial cells (ECs) and DCs. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
基金：
National Natural Science Foundations of ChinaNational Natural Science Foundation of China [81270354, 81470420]
第一作者机构：[1]Huazhong Univ Sci & Technol, Union Hosp, Inst Cardiol, Lab Cardiovasc Immunol, Wuhan 430022, Peoples R China;
通讯作者：
通讯机构：[1]Huazhong Univ Sci & Technol, Union Hosp, Inst Cardiol, Lab Cardiovasc Immunol, Wuhan 430022, Peoples R China;[5]Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Lab Cardiovasc Immunol,Inst Cardiol, 1277 Jie Fang Ave, Wuhan 430022, Peoples R China
推荐引用方式(GB/T 7714)：
Yu Kunwu,Dong Qian,Mao Xiaobo,et al.Disruption of the TSLP-TSLPR-LAP signaling between epithelial and dendritic cells through hyperlipidemia contributes to regulatory T-Cell defects in atherosclerotic mice[J].ATHEROSCLEROSIS.2015,238(2):278-288.doi:10.1016/j.atherosclerosis.2014.12.019.
APA：
Yu, Kunwu,Dong, Qian,Mao, Xiaobo,Meng, Kai,Zhao, Xiaoqi...&Zeng, Qiutang.(2015).Disruption of the TSLP-TSLPR-LAP signaling between epithelial and dendritic cells through hyperlipidemia contributes to regulatory T-Cell defects in atherosclerotic mice.ATHEROSCLEROSIS,238,(2)
MLA：
Yu, Kunwu,et al."Disruption of the TSLP-TSLPR-LAP signaling between epithelial and dendritic cells through hyperlipidemia contributes to regulatory T-Cell defects in atherosclerotic mice".ATHEROSCLEROSIS 238..2(2015):278-288
