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Single-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells.

作者信息

Depuydt Marie A C, Schaftenaar Frank H, Prange Koen H M, Boltjes Arjan, Hemme Esmeralda, Delfos Lucie, de Mol Jill, de Jong Maaike J M, Bernabé Kleijn Mireia N A, Peeters Judith A H M, Goncalves Lauren, Wezel Anouk, Smeets Harm J, de Borst Gert J, Foks Amanda C, Pasterkamp Gerard, de Winther Menno P J, Kuiper Johan, Bot Ilze, Slütter Bram

机构信息

Leiden Academic Centre for Drug Research, Division of Biotherapeutics, Leiden University, Leiden, the Netherlands.

Amsterdam University Medical Centers, University of Amsterdam, Experimental Vascular Biology, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam, the Netherlands.

出版信息

Nat Cardiovasc Res. 2023;2(2):112-125. doi: 10.1038/s44161-022-00208-4. Epub 2023 Jan 30.

DOI:10.1038/s44161-022-00208-4
PMID:38665903
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11041750/
Abstract

Atherosclerosis is a lipid-driven chronic inflammatory disease; however, whether it can be classified as an autoimmune disease remains unclear. In this study, we applied single-cell T cell receptor seqencing (scTCR-seq) on human carotid artery plaques and matched peripheral blood mononuclear cell samples to assess the extent of TCR clonality and antigen-specific activation within the various T cell subsets. We observed the highest degree of plaque-specific clonal expansion in effector CD4 T cells, and these clonally expanded T cells expressed genes such as , and , indicative of recent TCR engagement, suggesting antigen-specific stimulation. CellChat analysis suggested multiple potential interactions of these effector CD4 T cells with foam cells. Finally, we integrated a published scTCR-seq dataset of the autoimmune disease psoriatic arthritis, and we report various commonalities between the two diseases. In conclusion, our data suggest that atherosclerosis has an autoimmune compondent driven by autoreactive CD4 T cells.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/e86a2555d6ff/44161_2022_208_Fig17_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/927904838579/44161_2022_208_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/43440ab46983/44161_2022_208_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/edff3563f4a5/44161_2022_208_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/d6e70c0d4941/44161_2022_208_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/9e22e541c50b/44161_2022_208_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/5e8d4047d6fb/44161_2022_208_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/1a185d21b7e1/44161_2022_208_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/71e8be91ed35/44161_2022_208_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/f6573d36f099/44161_2022_208_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/8310bfdba04e/44161_2022_208_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/52d2ba17feca/44161_2022_208_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/85ccfdaa0d87/44161_2022_208_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/f7a97a45e823/44161_2022_208_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/77890620dd38/44161_2022_208_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/6f4c063809da/44161_2022_208_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/83a95e584dc5/44161_2022_208_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/e86a2555d6ff/44161_2022_208_Fig17_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/927904838579/44161_2022_208_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/43440ab46983/44161_2022_208_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/edff3563f4a5/44161_2022_208_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/d6e70c0d4941/44161_2022_208_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/9e22e541c50b/44161_2022_208_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/5e8d4047d6fb/44161_2022_208_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/1a185d21b7e1/44161_2022_208_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/71e8be91ed35/44161_2022_208_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/f6573d36f099/44161_2022_208_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/8310bfdba04e/44161_2022_208_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/52d2ba17feca/44161_2022_208_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/85ccfdaa0d87/44161_2022_208_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/f7a97a45e823/44161_2022_208_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/77890620dd38/44161_2022_208_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/6f4c063809da/44161_2022_208_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/83a95e584dc5/44161_2022_208_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba3/11041750/e86a2555d6ff/44161_2022_208_Fig17_ESM.jpg

相似文献

[1]
Single-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells.

Nat Cardiovasc Res. 2023

[2]
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[5]
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[8]
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[9]
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[10]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease.

Nat Cardiovasc Res. 2022-5

[2]
Immunodominant MHC-II (Major Histocompatibility Complex II) Restricted Epitopes in Human Apolipoprotein B.

Circ Res. 2022-7-22

[3]
Immunization using ApoB-100 peptide-linked nanoparticles reduces atherosclerosis.

JCI Insight. 2022-6-8

[4]
Human Coronary Plaque T Cells Are Clonal and Cross-React to Virus and Self.

Circ Res. 2022-5-13

[5]
Single-Cell Transcriptional Profiling Reveals Signatures of Helper, Effector, and Regulatory MAIT Cells during Homeostasis and Activation.

J Immunol. 2022-3-1

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GIANA allows computationally-efficient TCR clustering and multi-disease repertoire classification by isometric transformation.

Nat Commun. 2021-8-4

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Nat Commun. 2021-2-17

[8]
Regulatory T Cell Stability and Plasticity in Atherosclerosis.

Cells. 2020-12-11

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Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics.

Circ Res. 2020-11-6

[10]
Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis.

Nat Commun. 2020-9-21

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