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CD39 as a metabolic rheostat of immunoregulation

Cellular & Molecular Immunology volume 22, pages 806–808 (2025)Cite this article

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The Original Article was published on 26 May 2025

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L. Zhang et al. proposed novel immunotherapeutic strategies to limit the progression of inflammatory bowel diseases by targeting the interplay between the membrane-bound CD39 molecule and cellular metabolism — specifically, by increasing regulatory T-cell function through the modulation of glucose metabolism and suppressing pathogenic proinflammatory Th17 responses via the modulation of oxidative metabolism.

The differentiation trajectories of single naive CD4⁺ or CD8⁺ T cells into various effector T-cell subsets (e.g., Th1, Th2, Th17, and cytotoxic T cells or induced regulatory T cells [iTregs]) and the generation of memory T cells require sustained energy consumption [1,2,3]. In the current issue of Cellular and Molecular Immunology, L. Zhang et al. reported that dysregulation of immunometabolism contributes to impaired immunoregulation in autoimmune/hyperinflammatory conditions, such as inflammatory bowel diseases (IBDs) [4]. Their study emphasized the metabolic interplay driven by CD39 expression in CD4⁺Foxp3⁺ Tregs and Th17 cells, two cell subsets known to be functionally impaired and proinflammatory, respectively, in the context of IBDs. They propose novel strategies aimed at restoring immune homeostasis and limiting hyperinflammation through the modulation of specific metabolic checkpoints.

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Acknowledgements

This study was supported by the CRUK Hepatocellular Carcinoma Expediter Network (HUNTER) Accelerator Award 2018 (Project 620 Id.122794) (VB), Associazione Italiana per la Ricerca sul Cancro (AIRC) IGV19939 (VB); Fondazione Italiana Sclerosi Multipla (FISM) onlus (cod.2015/RVsingle/04 and 2019/RVsingle/053) (VB); AIRC-IG 2023 (ID 29244) (SS), Ministero della Salute (PNRR-MAD-2022-12375947) (SS); and the European Union - Next Generation EU in the context of the National Recovery and Resilience Plan, Investment Partenariato Esteso PE8 “Conseguenze e sfide dell’invecchiamento”, Project Age-It (Aging Well in an Aging Society) (SS).

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  1. Istituto Pasteur Italia and Sapienza Università di Roma, Rome, Italy

    Vincenzo Barnaba

  2. Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Institute Pasteur-Italia, Rome, Italy

    Silvano Sozzani

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  1. Vincenzo Barnaba
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  2. Silvano Sozzani
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Correspondence to Vincenzo Barnaba.

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Barnaba, V., Sozzani, S. CD39 as a metabolic rheostat of immunoregulation. Cell Mol Immunol 22, 806–808 (2025). https://doi.org/10.1038/s41423-025-01302-w

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