Atherosclerosis, the pathology underlying heart attacks, strokes and peripheral artery disease, is a chronic inflammatory disease of the artery wall initiated by elevated low-density lipoprotein (LDL) cholesterol levels. LDL accumulates in the artery wall, where it can become oxidized to oxLDL. T cell responses to ApoB, a core protein found in LDL and other lipoproteins, are detectable in healthy mice and people. Most of the ApoB-specific CD4T cells are FoxP3+ regulatory T cells (Treg). In the course of atherosclerosis development, the number of ApoB-reactive T cells expands. At the same time, their phenotype changes, showing cell surface markers, transcription factors and transcriptomes resembling other T-helper lineages like Th17, Th1 and follicular helper (TFH) cells. TFH cells enter germinal centers and provide T cell help to B cells, enabling antibody isotype switch from IgM to IgG and supporting affinity maturation. In people and mice with atherosclerosis, IgG and IgM antibodies to oxLDL are detectable. Higher IgM antibody titers to oxLDL are associated with less, IgG antibodies with more atherosclerosis. Thus, both T and B cells play critical roles in atherosclerosis. Modifying the adaptive immune response to ApoB holds promise for preventing atherosclerosis and reducing disease burden.
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October 2020
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Cover Image
Centrosomes are microtubule-organizing centres required for the asymmetric division of neural stem cells, which support neurodevelopment, as discussed in a mini-review by Robinson and colleagues (pages 2101–2115) In the cover image, microtubules are shown in yellow and neural stem cells (aPKC) are magenta. Image provided by Dorothy Lerit.
Review Article|
September 01 2020
Role of the adaptive immune system in atherosclerosis
Klaus Ley
Center for Autoimmunity and Inflammation, Inflammation Biology Laboratory, La Jolla Institute for Immunology, 9420 Athena Circle Drive, La Jolla, CA 92037, U.S.A.
Correspondence: Klaus Ley (klaus@lji.org)
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem Soc Trans (2020) 48 (5): 2273–2281.
Citation
Klaus Ley; Role of the adaptive immune system in atherosclerosis. Biochem Soc Trans 30 October 2020; 48 (5): 2273–2281. doi: https://doi.org/10.1042/BST20200602
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