The immune-modulatory metabolite itaconate is secreted by myeloid-derived suppressor cells and taken up by CD8+ T cells to suppress their proliferation and function. In mice, blocking itaconate production enhances the efficacy of immune checkpoint blockade.
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References
Veglia, F., Sanseviero, E. & Gabrilovich, D. I. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat. Rev. Immunol. 67, 485–498 (2021). A review article that presents the characteristics of MDSCs.
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Hooftman, A. & O'Neill, L. A. J. The immunomodulatory potential of the metabolite itaconate. Trends Immunol. 40, 687–698 (2019). A review article that presents the immunomodulatory activities of itaconate and includes a timeline on the history of itaconate.
Michelucci, A. et al. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc. Natl Acad. Sci. USA 110, 7820–7825 (2013). This paper reports the discovery of IRG1 as the enzyme that catalyses the conversion of cis-aconitate to itaconic acid in mammals.
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This is a summary of: Zhao, H. et al. Myeloid-derived itaconate suppresses cytotoxic CD8+ T cells and promotes tumour growth. Nat. Metab. https://doi.org/10.1038/s42255-022-00676-9 (2022).
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Suppression of CD8+ T cells by the metabolite itaconate. Nat Metab 4, 1626–1627 (2022). https://doi.org/10.1038/s42255-022-00694-7
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DOI: https://doi.org/10.1038/s42255-022-00694-7
