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Updated: Dec 8, 2025

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
Published on: March 28, 2025
Histone Deacetylase 3 Couples Mitochondria to Drive IL-1β-Dependent Inflammation by Configuring Fatty Acid Oxidation
Zhexu Chi1, Sheng Chen2, Ting Xu1
1Institute of Immunology, and Department of Orthopaedic Surgery of the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China.
Abstract:
Immune cell function depends on specific metabolic programs dictated by mitochondria, including nutrient oxidation, macromolecule synthesis, and post-translational modifications. Mitochondrial adaptations have been linked to acute and chronic inflammation, but the metabolic cues and precise mechanisms remain unclear. Here we reveal that histone deacetylase 3 (HDAC3) is essential for shaping mitochondrial adaptations for IL-1β production in macrophages through non-histone deacetylation. In vivo, HDAC3 promoted lipopolysaccharide-induced acute inflammation and high-fat diet-induced chronic inflammation by enhancing NLRP3-dependent caspase-1 activation. HDAC3 configured the lipid profile in stimulated macrophages and restricted fatty acid oxidation (FAO) supported by exogenous fatty acids for mitochondria to acquire their adaptations and depolarization. Rather than affecting nuclear gene expression, HDAC3 translocated to mitochondria to deacetylate and inactivate an FAO enzyme, mitochondrial trifunctional enzyme subunit α. HDAC3 may serve as a controlling node that balances between acquiring mitochondrial adaptations and sustaining their fitness for IL-1β-dependent inflammation.
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