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Liver kinase B1 (LKB1) staves off γδ T-cell-mediated autoimmune liver disease

Cellular & Molecular Immunology volume 21, pages 641–642 (2024)Cite this article

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T lymphocytes expressing γδ T-cell receptors (TCRs) display innate-like effector functions that are preprogrammed during their development in the thymus. This maturation process is regulated by the flow of molecules through various metabolic pathways in a manner that remains incompletely understood. Xiao et al. provided evidence that the metabolic regulator liver kinase B1 (LKB1) promotes the thymic generation of γδ T cells with a balanced effector cytokine production profile that protects the liver from autoimmune attack [1].

γδ T lineage cells play critical roles in host defense against pathogens and in maintaining tissue homeostasis [2]. In sharp contrast to αβ T cells, which acquire their effector functions after antigen encounter in the periphery, many γδ T cells acquire their effector functions during their development in the thymus [3, 4]. Two subsets of preprogrammed γδ T-cell effectors have been identified: interferon (IFN)-γ-producing γδ T (γδT1) cells, which promote pathogen and tumor surveillance, and interleukin (IL)-17-producing γδ T (γδT17) cells, which protect the host from extracellular microorganisms and contribute to the pathogenesis of autoimmune diseases. Understanding the molecular mechanisms that control thymic γδ T-cell effector diversification may offer new therapeutic opportunities for human diseases.

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Funding

This work was supported by American Heart Association predoctoral fellowship 24PRE1191939 (to YW), the National Institutes of Health grant RO1AI139046 (to LVK), and the American Heart Association grant 19TPA34910078 (to LVK).

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Authors and Affiliations

  1. Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA

    Yiwen Wang, Lan Wu & Luc Van Kaer

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  1. Yiwen Wang
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  2. Lan Wu
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  3. Luc Van Kaer
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Yiwen Wang reviewed and edited the text and made the figure; Lan Wu reviewed and edited the text; Luc Van Kaer wrote the first draft and reviewed and edited the text.

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Correspondence to Luc Van Kaer.

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Competing interests

LVK is a member of the scientific advisory board of Isu Abxis Co., Ltd. (South Korea). The other authors declare no competing interests.

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Wang, Y., Wu, L. & Van Kaer, L. Liver kinase B1 (LKB1) staves off γδ T-cell-mediated autoimmune liver disease. Cell Mol Immunol 21, 641–642 (2024). https://doi.org/10.1038/s41423-024-01172-8

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