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Metabolic Regulation of Inflammation: Exploring the Potential Benefits of Itaconate in Autoimmune Disorders

Yin Luo1, Li-Yan Jiang1, Zhe-Zhen Liao1

  • 1The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

Immunology
|November 14, 2024
PubMed

Itaconic acid and its metabolites have demonstrated significant therapeutic potential in various immune diseases. Originating from the tricarboxylic acid cycle in immune cells, itaconic acid can modulate immune responses, diminish inflammation, and combat oxidative stress. Recent research has uncovered multiple mechanisms through which itaconic acid exerts its effects, including the inhibition of inflammatory cytokine production, activation of anti-inflammatory pathways, and modulation of immune cell function by regulating cellular metabolism. Cellular actions are influenced by the modulation of metabolic pathways, such as inhibiting succinate dehydrogenase (SDH) activity or glycolysis, activation of nuclear-factor-E2-related factor 2 (Nrf2), boosting cellular defences against oxidative stress, and suppression of immune cell inflammation through the NF-κB pathway. This comprehensive review discusses the initiation, progression, and mechanisms of action of itaconic acid and its metabolites, highlighting their modulatory effects on various immune cell types. Additionally, it examines their involvement in immune disease like rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, and autoimmune hepatitis, offering greater understanding for creating new therapies for these ailments.

Keywords:
autoimmune diseaseitaconic acidmetabolic pathways

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