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Lipid metabolism in T cell signaling and function

Nature Chemical Biology volume 18, pages 470–481 (2022)Cite this article

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Abstract

T cells orchestrate adaptive immunity against pathogens and other immune challenges, but their dysfunction can also mediate the pathogenesis of cancer and autoimmunity. Metabolic adaptation in response to immunological and microenvironmental signals contributes to T cell function and fate decision. Lipid metabolism has emerged as a key regulator of T cell responses, with selective lipid metabolites serving as metabolic rheostats to integrate environmental cues and interplay with intracellular signaling processes. Here, we discuss how extracellular, de novo synthesized and membrane lipids orchestrate T cell biology. We also describe the roles of lipids as regulators of intracellular signaling at the levels of transcriptional, epigenetic and post-translational regulation in T cells. Finally, we summarize therapeutic targeting of lipid metabolism and signaling, and conclude with a discussion of important future directions. Understanding the molecular and functional interplay between lipid metabolism and T cell biology will ultimately inform therapeutic intervention for human disease.

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Fig. 1: Extracellular lipids in T cell differentiation and functional adaptation.
Fig. 2: Regulation of lipid metabolism by immunological signals.
Fig. 3: Intracellular lipid metabolism in T cells.
Fig. 4: Membrane lipids coordinate signaling in T cells.
Fig. 5: Lipid-dependent post-translational modifications orchestrate T cell responses.

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Acknowledgements

This work was supported by US National Institutes of Health grants AI105887, AI131703, AI140761, AI150241, AI150514 and CA253188, Alliance for Lupus Research grant, and ALSAC (to H.C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. These authors contributed equally: Seon Ah Lim, Wei Su.

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  1. Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Seon Ah Lim, Wei Su, Nicole M. Chapman & Hongbo Chi

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S.A.L. and W.S. conceived, designed and wrote the manuscript. N.M.C. co-wrote the manuscript. H.C. co-wrote the manuscript and provided overall direction.

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Correspondence to Hongbo Chi.

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H.C. is a consultant for Kumquat Biosciences.

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Lim, S.A., Su, W., Chapman, N.M. et al. Lipid metabolism in T cell signaling and function. Nat Chem Biol 18, 470–481 (2022). https://doi.org/10.1038/s41589-022-01017-3

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