The DOI matches its Crossref record; 99 of the 99 references it cites were found in a registry or an index.
Lactate Buildup at the Site of Chronic Inflammation Promotes Disease by Inducing CD4+ T Cell Metabolic Rewiring
Open accessAbstract
Accumulation of lactate in the tissue microenvironment is a feature of both inflammatory disease and cancer.Here, we assess the response of immune cells to lactate in the context of chronic inflammation.We report that lactate accumulation in the inflamed tissue contributes to the upregulation of the lactate transporter SLC5A12 by human CD4 + T cells.SLC5A12-mediated lactate uptake into CD4 + T cells induces a reshaping of their effector phenotype, resulting in increased IL17 production via nuclear PKM2/STAT3 and enhanced fatty acid synthesis.It also leads to CD4 + T cell retention in the inflamed tissue as a consequence of reduced glycolysis and enhanced fatty acid synthesis.Furthermore, antibody-mediated blockade of SLC5A12 ameliorates the disease severity in a murine model of arthritis.Finally, we propose that lactate/SLC5A12-induced metabolic reprogramming is a distinctive feature of lymphoid synovitis in rheumatoid arthritis patients and a potential therapeutic target in chronic inflammatory disorders.
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Cites
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Cited by
Lactate metabolism in human health and disease
Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., Zou, Y., Wang, J.-X., Wang, Z., & Yu, T. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01151-3 · Cited by 1,454
Lactate: the ugly duckling of energy metabolism
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Lactate modulation of immune responses in inflammatory versus tumour microenvironments
Certo, M., Tsai, C.-H., Pucino, V., Ho, P.-C., & Mauro, C. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-0406-2 · Cited by 924
Self-citationLactate in the tumour microenvironment: From immune modulation to therapy
Wang, Z.-H., Peng, W.-B., Zhang, P., Yang, X.-P., & Zhou, Q. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103627 · Cited by 528
Metabolic modeling of single Th17 cells reveals regulators of autoimmunity
Wagner, A., Wang, C., Fessler, J., DeTomaso, D., Avila-Pacheco, J., Kaminski, J., Zaghouani, S., Christian, E., Thakore, P., Schellhaass, B., et al. (2021) · Cell · doi:10.1016/j.cell.2021.05.045 · Cited by 524
Metadata
- Authors
- Pucino, V., Certo, M., Bulusu, V., Cucchi, D., Goldmann, K., Pontarini, E., Haas, R., Smith, J., Headland, S. E., Blighe, K., Ruscica, M., Humby, F., Lewis, M. J., Kamphorst, J. J., Bombardieri, M., Pitzalis, C., & Mauro, C.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 30
- Issue
- 6
- Pages
- 1055-1074.e8
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2984000721
- Cited by
- 530
- References
- 99
- FWCI
- 30.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Pucino, V., Certo, M., Bulusu, V., Cucchi, D., Goldmann, K., Pontarini, E., Haas, R., Smith, J., Headland, S. E., Blighe, K., Ruscica, M., Humby, F., Lewis, M. J., Kamphorst, J. J., Bombardieri, M., Pitzalis, C., & Mauro, C. (2019). Lactate Buildup at the Site of Chronic Inflammation Promotes Disease by Inducing CD4+ T Cell Metabolic Rewiring. Cell Metabolism. https://doi.org/10.1016/j.cmet.2019.10.004
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
