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A recent study led by Anaísa V Ferreira and Jorge Domínguez-Andrés from the Department of Internal Medicine, has shed new light on the role of Dimethyl Itaconate (DMI), a derivative of the endogenous metabolite itaconate, in immune responses. The study was published in Cell Reports on 16 June 2023.
Itaconate, an immunomodulatory metabolite produced by immune cells under microbial stimulation and certain pro-inflammatory conditions, is known to trigger antioxidant and anti-inflammatory responses. DMI, widely used as an alternative to the endogenous metabolite, has been previously linked to the suppression of inflammation.
The researchers found that DMI can induce long-term transcriptional, epigenomic, and metabolic changes, characteristic of trained immunity. This leads to increased responsiveness to microbial ligands stimulation. Mice treated with DMI showed increased survival to infection with the bacteria Staphylococcus aureus. Additionally, itaconate levels in human plasma correlated with enhanced ex vivo pro-inflammatory cytokine production.
However, the study also reveales a dichotomy in DMI's effects. While it displays short-term anti-inflammatory characteristics, it also has the capacity to induce long-term trained immunity. This pro-and anti-inflammatory dichotomy of DMI is likely to induce complex immune responses and should be contemplated when considering itaconate derivatives in a therapeutic context.
The researchers plan to further investigate the complex immune responses induced by DMI and its potential therapeutic applications.
Read the study here
Anaísa V. Ferreira, Sarantos Kostidis, Laszlo A. Groh,Valerie A.C.M. Koeken, Mariolina Bruno, Ilayda Baydemir, Gizem Kilic, Özlem Bulut, Theano Andriopoulou, Victoria Spanou, Kalliopi D. Synodinou, Theologia Gkavogianni, Simone J.C.F.M. Moorlag, L. Charlotte de Bree, Vera P. Mourits, Vasiliki Matzaraki, Werner J.H. Koopman, Frank L. van de Veerdonk, Georgios Renieris, Martin Giera, Evangelos J. Giamarellos-Bourboulis, Boris Novakovic, and Jorge Domínguez-Andres (2023). Dimethyl itaconate induces long-term innate immune responses and confers protection against infection. Cell Reports; Published:June 16, 2023; DOI:https://doi.org/10.1016/j.celrep.2023.112658
