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      ApoB-Specific CD4 + T Cells in Mouse and Human Atherosclerosis

      review-article
      1 , 2 , 3 , 1 , 2 , 1 , 2 , *
      Cells
      MDPI
      atherosclerosis, immunity, autoimmunity, apolipoprotein B, LDL, T cells

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          Abstract

          Atherosclerosis is a chronic inflammatory condition of the arterial wall that leads to the formation of vessel-occluding plaques within the subintimal space of middle-sized and larger arteries. While traditionally understood as a myeloid-driven lipid-storage disease, growing evidence suggests that the accumulation of low-density lipoprotein cholesterol (LDL-C) ignites an autoimmune response with CD4 + T-helper (T H) cells that recognize self-peptides from Apolipoprotein B (ApoB), the core protein of LDL-C. These autoreactive CD4 + T cells home to the atherosclerotic plaque, clonally expand, instruct other cells in the plaque, and induce clinical plaque instability. Recent developments in detecting antigen-specific cells at the single cell level have demonstrated that ApoB-reactive CD4 + T cells exist in humans and mice. Their phenotypes and functions deviate from classical immunological concepts of distinct and terminally differentiated T H immunity. Instead, ApoB-specific CD4 + T cells have a highly plastic phenotype, can acquire several, partially opposing and mixed transcriptional programs simultaneously, and transit from one T H subset into another over time. In this review, we highlight adaptive immune mechanisms in atherosclerosis with a focus on CD4 + T cells, introduce novel technologies to detect ApoB-specific CD4 + T cells at the single cell level, and discuss the potential impact of ApoB-driven autoimmunity in atherosclerosis.

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          Most cited references264

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          Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.

          Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.
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            Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction

            Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis.
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              Regulatory T cells and immune tolerance.

              Regulatory T cells (Tregs) play an indispensable role in maintaining immunological unresponsiveness to self-antigens and in suppressing excessive immune responses deleterious to the host. Tregs are produced in the thymus as a functionally mature subpopulation of T cells and can also be induced from naive T cells in the periphery. Recent research reveals the cellular and molecular basis of Treg development and function and implicates dysregulation of Tregs in immunological disease.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                19 February 2021
                February 2021
                : 10
                : 2
                : 446
                Affiliations
                [1 ]Department of Cardiology and Angiology I, University Heart Center Freiburg, Hugstetterstraße 55, 79106 Freiburg, Germany; timoteo.marchini@ 123456universitaets-herzzentrum.de (T.M.); sophie.hansen@ 123456universitaets-herzzentrum.de (S.H.)
                [2 ]Faculty of Medicine, University of Freiburg, Breisacherstraße 153, 79110 Freiburg, Germany
                [3 ]Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Junín 954, C1113 AAD Buenos Aires, Argentina
                Author notes
                [* ]Correspondence: dennis.wolf@ 123456universitaets-herzzentrum.de ; Tel.: +49-761-270-70380; Fax: +49-761-270-70060
                Author information
                https://orcid.org/0000-0002-5758-4348
                Article
                cells-10-00446
                10.3390/cells10020446
                7922692
                33669769
                0b7af9dc-2dfb-4fde-af13-930dc3f73765
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 February 2021
                : 17 February 2021
                Categories
                Review

                atherosclerosis,immunity,autoimmunity,apolipoprotein b,ldl,t cells

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