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  • Review Article
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Metabolic adaptations of tissue-resident immune cells

Abstract

Unlike other cells in the body, immune cells have to be able to enter and adapt to life within diverse tissues. Immune cells develop within dedicated immune system organs, such as the bone marrow, thymus and lymphoid tissues, but also inhabit other tissues, wherein they not only provide defense against infection and malignancies but also contribute to homeostatic tissue function. Because different tissues have widely divergent metabolic rates and fuel requirements, this raises interesting questions about the adaptation of immune cells in specific tissues. When immune cells take up residence in different tissues, they develop a transcriptional signature that reflects adaptation to life and function within that tissue. Genes encoding metabolic-pathway proteins are strongly represented within these signatures, reflective of the importance of metabolic adaptation to tissue residence. In this Review, we discuss the available data on the metabolic adaptation of immune cells to life in different tissue sites, within the broader framework of how functional adaptation versus maladaptation in the niche can affect tissue homeostasis.

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Fig. 1: Tissue-specific metabolic adaptations of macrophages.
Fig. 2: Metabolic adaptations and maladaptations of VAT macrophages.
Fig. 3: Immune cell cross-talk maintains adipose tissue homeostasis.
Fig. 4: Rewiring of gut-resident macrophages by a commensal metabolite.

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Acknowledgements

We thank E. Pearce and members of the Pearce laboratories for advice and discussions. Supported by grants from the US National Institutes of Health (AI110481 to E.J.P.) and the Alexander von Humboldt Foundation (A.C.) and by the Max Planck Society.

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Correspondence to Edward J. Pearce.

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E.J.P. is a founder of Rheos Medicines.

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Caputa, G., Castoldi, A. & Pearce, E.J. Metabolic adaptations of tissue-resident immune cells. Nat Immunol 20, 793–801 (2019). https://doi.org/10.1038/s41590-019-0407-0

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