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  • Review Article
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A cardioimmunologist’s toolkit: genetic tools to dissect immune cells in cardiac disease

Nature Reviews Cardiology volume 19, pages 395–413 (2022)Cite this article

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Abstract

Cardioimmunology is a field that encompasses the immune cells and pathways that modulate cardiac function in homeostasis and regulate the temporal balance between tissue injury and repair in disease. Over the past two decades, genetic fate mapping and high-dimensional sequencing techniques have defined increasing functional heterogeneity of innate and adaptive immune cell populations in the heart and other organs, revealing a complexity not previously appreciated and challenging established frameworks for the immune system. Given these rapid advances, understanding how to use these tools has become crucial. However, cardiovascular biologists without immunological expertise might not be aware of the strengths and caveats of immune-related tools and how they can be applied to examine the pathogenesis of myocardial diseases. In this Review, we guide readers through case-based examples to demonstrate how tool selection can affect data quality and interpretation and we provide critical analysis of the experimental tools that are currently available, focusing on their use in models of ischaemic heart injury and heart failure. The goal is to increase the use of relevant immunological tools and strategies among cardiovascular researchers to improve the precision, translatability and consistency of future studies of immune cells in cardiac disease.

Key points

  • Various tissue-resident interstitial immune cell populations live in the heart and promote homeostatic functions.

  • Resident cardiac immune cells are not homogeneous and often contain subpopulations with different lifecycles dictated by a balance between in situ proliferation, cell death and replacement by circulating precursors.

  • Unique lifecycles often predict unique origins, transcriptional signatures and functions; understanding how to target these levels of heterogeneity can reveal novel mechanisms of disease pathogenesis.

  • We present a detailed case study summarizing the latest advances in cardioimmunology to provide context and explanation to guide readers without an immunological background through novel targeting and cell tracking approaches.

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Fig. 1: The M1/M2 paradigm conflates macrophage heterogeneity.
Fig. 2: Reciprocal bone marrow chimeras to assess intrinsic or extrinsic effects of immune cells.
Fig. 3: Probing immune cell transcriptomic data sets.
Fig. 4: Isolation of immune cell subsets and characterization of gene expression.

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Acknowledgements

The authors receive support from the Canadian Institutes of Health Research (S.E. PJT364831, AW. FRN 413754), Heart and Stroke Foundation (S.E.), Ted Rogers Centre for Heart Research (S.E., H.H.) and Peter Munk Cardiac Centre (S.E.).

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Authors and Affiliations

  1. Toronto General Hospital Research Institute, University Health Network (UHN), Toronto, ON, Canada

    Anthony Wong, Homaira Hamidzada & Slava Epelman

  2. Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada

    Anthony Wong, Homaira Hamidzada & Slava Epelman

  3. Department of Immunology, University of Toronto, Toronto, ON, Canada

    Anthony Wong, Homaira Hamidzada & Slava Epelman

  4. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Slava Epelman

  5. Peter Munk Cardiac Centre, University Health Network (UHN), Toronto, ON, Canada

    Slava Epelman

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A.W. and H.H. researched data for the article. All the authors contributed to the discussion of content, wrote the article and reviewed and edited the manuscript before submission.

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Correspondence to Slava Epelman.

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Nature Reviews Cardiology thanks Sumanth Prabhu, Susanne Sattler and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

Epelman lab transcriptomics data sets: https://www.epelmanlab.com/resources

Human heart cell atlas: https://www.heartcellatlas.org/

ImmGen Consortium: https://www.immgen.org

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Wong, A., Hamidzada, H. & Epelman, S. A cardioimmunologist’s toolkit: genetic tools to dissect immune cells in cardiac disease. Nat Rev Cardiol 19, 395–413 (2022). https://doi.org/10.1038/s41569-022-00701-0

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