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Comment
. 2024 Nov 12;121(46):e2419751121.
doi: 10.1073/pnas.2419751121. Epub 2024 Nov 6.

Linking metabolic and epigenetic changes in immune tolerance

Frederick J Sheedy  1 , Eva Kaufmann  2
Affiliations
Comment

Linking metabolic and epigenetic changes in immune tolerance

Frederick J Sheedy et al. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

Competing interests statement:The authors declare no competing interest.

Figures

Fig. 1.
Fig. 1.
Epigenetic modulation of proinflammatory gene loci by discrete immune tolerance- or trained immunity-inducing stimuli. The IL6 locus and other proinflammatory innate immune genes are hypermethylated in response to severe infection in a process driven by bacterial ligands which alter cellular immunometabolism. Chiefly, accumulation of the TCA-derived intermediate itaconate is linked to relocation of the DNA-methylation enzyme DNMT3B to the nucleus, alongside citrate synthase 1 (CS1) and isocitrate dehydrogenase (IDH3) (1). In an opposing way, exposure to certain stimuli including fungal β-glucans and the BCG vaccine can alter the cellular metabolism leading to the accumulation of the TCA-metabolite fumarate. This is linked to the activation of chromatin-modifying enzymes like KDM5 and SET7D which leave specific histone marks to enhance gene expression, resulting in trained immunity (, , –11). Importantly, histone modifications have also been described in tolerance models (3, 4, 6). Possibly, each stimulus induces both histone modifications and DNA methylation, but the aspect ratio and targeted genes are directive for the ensuing phenotypic function. Figure created with Biorender.
See this image and copyright information in PMC

Comment on

References

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