Universität zu Köln

Winkels, Holger and Wolf, Dennis ORCID: 0000-0003-1525-4348 (2021). Heterogeneity of T Cells in Atherosclerosis Defined by Single-Cell RNA-Sequencing and Cytometry by Time of Flight. Arterioscler. Thromb. Vasc. Biol., 41 (2). S. 549 - 564. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1524-4636

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Abstract

The infiltration and accumulation of pro- and anti-inflammatory leukocytes within the intimal layer of the arterial wall is a hallmark of developing and progressing atherosclerosis. While traditionally perceived as macrophage- and foam cell-dominated disease, it is now established that atherosclerosis is a partial autoimmune disease that involves the recognition of peptides from ApoB (apolipoprotein B), the core protein of LDL (low-density lipoprotein) cholesterol particles, by CD4(+) T-helper cells and autoantibodies against LDL and ApoB. Autoimmunity in the atherosclerotic plaque has long been understood as a pathogenic T-helper type-1 driven response with proinflammatory cytokine secretion. Recent developments in high-parametric cell immunophenotyping by mass cytometry, single-cell RNA-sequencing, and in tools exploring antigen-specificity have established the existence of several unforeseen layers of T-cell diversity with mixed T(H)1 and T regulatory cells transcriptional programs and unpredicted fates. These findings suggest that pathogenic ApoB-reactive T cells evolve from atheroprotective and immunosuppressive CD4(+) T regulatory cells that lose their protective properties over time. Here, we discuss T-cell heterogeneity in atherosclerosis with a focus on plasticity, antigen-specificity, exhaustion, maturation, tissue residency, and its potential use in clinical prediction.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Winkels, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Dennis UNSPECIFIED orcid.org/0000-0003-1525-4348 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-581406
DOI:	10.1161/ATVBAHA.120.312137
Journal or Publication Title:	Arterioscler. Thromb. Vasc. Biol.
Volume:	41
Number:	2
Page Range:	S. 549 - 564
Date:	2021
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1524-4636
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SMOOTH-MUSCLE-CELLS; MACROPHAGE ACCUMULATION; REDUCES ATHEROSCLEROSIS; INTERFERON-GAMMA; TREG CELLS; HELPER; EXPRESSION; PLAQUE; HYPERCHOLESTEROLEMIA; IMMUNITY Multiple languages Hematology; Peripheral Vascular Disease Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58140