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Disruption of the TSLP-TSLPR-LAP signaling between epithelial and dendritic cells through hyperlipidemia contributes to regulatory T-Cell defects in atherosclerotic mice.
Atherosclerosis 2015; 238(2):278-88A

Abstract

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-1β 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.

Authors+Show Affiliations

Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Department of Cardiology, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, China.Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China. Electronic address: bushyukunwu@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25544178

Citation

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, vol. 238, no. 2, 2015, pp. 278-88.
Yu K, Dong Q, Mao X, 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. 2015;238(2):278-88.
Yu, K., Dong, Q., Mao, X., Meng, K., Zhao, X., Ji, Q., ... Zeng, Q. (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), pp. 278-88. doi:10.1016/j.atherosclerosis.2014.12.019.
Yu K, 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. 2015;238(2):278-88. PubMed PMID: 25544178.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disruption of the TSLP-TSLPR-LAP signaling between epithelial and dendritic cells through hyperlipidemia contributes to regulatory T-Cell defects in atherosclerotic mice. AU - Yu,Kunwu, AU - Dong,Qian, AU - Mao,Xiaobo, AU - Meng,Kai, AU - Zhao,Xiaoqi, AU - Ji,Qingwei, AU - Wu,Bangwei, AU - Zhong,Yucheng, AU - Zhu,Zhengfeng, AU - Liu,Yuzhou, AU - Zhang,Wei, AU - Tony,Hasahya, AU - Shi,Huairui, AU - Zeng,Qiutang, Y1 - 2014/12/18/ PY - 2014/11/04/received PY - 2014/12/09/revised PY - 2014/12/09/accepted PY - 2014/12/30/entrez PY - 2014/12/30/pubmed PY - 2015/9/22/medline KW - Atherosclerosis KW - Dendritic cell KW - Low-density lipoprotein (LDL) KW - Regulatory T-cell (Treg) KW - Thymic stromal lymphopoietin (TSLP) SP - 278 EP - 88 JF - Atherosclerosis JO - Atherosclerosis VL - 238 IS - 2 N2 - 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-1β 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. SN - 1879-1484 UR - https://www.unboundmedicine.com/medline/citation/25544178/Disruption_of_the_TSLP_TSLPR_LAP_signaling_between_epithelial_and_dendritic_cells_through_hyperlipidemia_contributes_to_regulatory_T_Cell_defects_in_atherosclerotic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(14)01639-6 DB - PRIME DP - Unbound Medicine ER -