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  • Review Article
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Adaptive immunity in atherosclerosis: mechanisms and future therapeutic targets

Abstract

Chronic inflammation drives the development of atherosclerosis, and adaptive immunity is deeply involved in this process. Initial studies attributed a pathogenic role to T cells in atherosclerosis, mainly owing to the proatherogenic role of the T-helper (TH)-1 cell subset, whereas the influence of TH2 and TH17 subsets is still debated. Today we know that T regulatory cells play a critical role in the protection against atherosclerotic lesion development and inflammation. In contrast to T cells, B cells were initially considered to be protective in atherosclerosis, assumingly through the production of protective antibodies against oxidized LDL. This concept has now been refined and proatherogenic roles of certain mature B cell subsets have been identified. We review the current knowledge about the role of various lymphocyte subsets in the development and progression of atherosclerosis and highlight future targets for immunomodulatory therapy.

Key Points

  • Adaptive immunity affects initiation and progression of atherosclerosis and develops when antigens such as oxidized LDL (oxLDL) and heat shock proteins are recognized by receptors on T and B cells

  • Interferon (IFN)-γ, interleukin (IL)-12, and IL-18 are proatherogenic cytokines associated with the T-helper (TH)-1 cell response and might be suitable targets for treatment of atherosclerosis

  • TH2-related cytokines can be either proatherogenic (IL-4) or antiatherogenic (IL-5, IL-33)

  • TH17 cells and their signature cytokine IL-17 have been described in the context of atherosclerosis, but their roles are still debated

  • T-regulatory (TREG) cells are the only T cell subset clearly identified as protective in atherosclerosis, and strategies aimed at improving the TREG-cell population are currently being pursued

  • B-1 cells produce natural and protective IgM antibodies, whereas conventional B-2 cells have been shown to be proatherogenic

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Figure 1: Differentiation, activation, and interactions between T cell subsets.
Figure 2: Potential mechanisms by which TREG cells influence atherosclerosis.
Figure 3: Potential role of B-cell subsets in atherosclerosis.
Figure 4: Emerging therapeutic strategies to fight atherosclerosis.

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Acknowledgements

This work was supported by Inserm, the Leducq Foundation, Agence Nationale de la Recherche and EU-FP7 TOLERAGE. O.H. was supported by a grant from the Fondation pour la Recherche Médicale.

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C. Lahoute and O. Herbin researched data for the article. All authors participated equally in writing the article, provided substantial contributions to the discussion of content, and reviewed and/or edited the manuscript before submission.

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Correspondence to Alain Tedgui.

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Lahoute, C., Herbin, O., Mallat, Z. et al. Adaptive immunity in atherosclerosis: mechanisms and future therapeutic targets. Nat Rev Cardiol 8, 348–358 (2011). https://doi.org/10.1038/nrcardio.2011.62

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