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231226s2023 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2023.109767
|2 doi
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|a pubmed25n1205.xml
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|a (DE-627)NLM361865775
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|a (NLM)37689092
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|a (PII)S1521-6616(23)00530-2
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
1 |
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|a Yu, Jian
|e verfasserin
|4 aut
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| 245 |
1 |
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|a Latency-associated peptide (LAP)+CD4+ regulatory T cells prevent atherosclerosis by modulating macrophage polarization
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|c 2023
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Revised 28.09.2023
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|a published: Print-Electronic
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|a Citation Status Publisher
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|a Copyright © 2023. Published by Elsevier Inc.
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|a RATIONALE: A persistent autoimmune and inflammatory response plays a critical role in the progression of atherosclerosis. The transcription factor forkhead box P3 (Foxp3)+CD4+ regulatory T cells (Foxp3+ Tregs) attenuate atherosclerosis. Latency-associated peptide (LAP)+CD4+ T cells are a new class of Tregs whose role in atherosclerosis is unknown
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|a OBJECTIVE: To investigate the function of CD4+LAP+ Tregs in inhibiting inflammation and preventing atherosclerosis
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|a METHODS AND RESULTS: Depletion of CD4+LAP+ Tregs results in aggravated inflammation and atherosclerotic lesions. Mechanistically, CD4+LAP+ Treg depletion was associated with decreased M2-like macrophages and increased Th1 and Th17 cells, characterized by increased unstable plaque promotion and decreased expression of inflammation-resolving factors in both arteries and immune organs. In contrast, adoptive transfer of CD4+LAP+ Tregs to ApoE-/- mice or CD4-/-ApoE-/- mice led to decreased atherosclerotic lesions. Compared with control animals, adoptive transfer of CD4+LAP+ Tregs induced M2-like macrophage differentiation within the atherosclerotic lesion and spleen, associated with increased collagen and α-SMA in plaques and decreased expression of MMP-2 and MMP-9. Mechanistic studies reveal that isolated CD4+LAP+ Tregs exhibit a tolerance phenotype, with increased expression of inhibitory cytokines and coinhibitory molecules. After coculture with CD4+LAP+ Tregs, monocytes/macrophages display typical features of M2 macrophages, including upregulated expression of CD206 and Arg-1 and decreased production of MCP-1, IL-6, IL-1β and TNF-α, which was almost abrogated by transwell and partially TGF-β1 neutralization. RNA-seq analysis showed different gene expression profiles between CD4+LAP+ Tregs and LAP-CD4+ T cells and between CD4+LAP+ Tregs of ApoE-/- mice and CD4+LAP+ Tregs of C57BL/6 mice, of which Fancd2 and IL4i1 may contribute to the powerful inhibitory properties of CD4+LAP+ Tregs. Furthermore, the number and the suppressive properties of CD4+LAP+ Tregs were impaired by oxLDL
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|a CONCLUSIONS: Our data indicate that the remaining CD4+LAP+ Tregs play a protective role in atherosclerosis by modulating monocyte/macrophage differentiation and regulatory factors, which may partly explain the protective effect of T cells tolerance in atherosclerosis. Moreover, adoptive transfer of CD4+LAP+ Tregs constitutes a novel approach to treat atherosclerosis
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|a Journal Article
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|a Atherosclerosis
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|a Latency-associated peptide
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|a M2-type macrophage
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| 650 |
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|a Regulatory T cells
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| 700 |
1 |
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|a Xu, Wenbin
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Dong, Qian
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Ji, Qingwei
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Cheng, Min
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Hu, Desheng
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Cai, Yifan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zeng, Qiutang
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yu, Kunwu
|e verfasserin
|4 aut
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| 773 |
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|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 255(2023) vom: 04. Okt., Seite 109767
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnas
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| 773 |
1 |
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|g volume:255
|g year:2023
|g day:04
|g month:10
|g pages:109767
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| 856 |
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|u http://dx.doi.org/10.1016/j.clim.2023.109767
|3 Volltext
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