Immunoregulatory actions of itaconate and its derivatives on inflammatory and antiviral pathways in macrophages (IMAGE)
Caption
Itaconate and its derivatives regulate immune signaling in activated macrophages by modulating both pro-inflammatory and anti-inflammatory pathways. 4-Octyl itaconate stabilizes NFE2L2 by alkylating KEAP1, inhibits STING1–IRF3 and TBK1 signaling, suppresses JAK1–STAT activation, blocks NLRP3 inflammasome assembly, and promotes TFEB-mediated lysosomal biogenesis. Endogenous itaconate can also enhance type I interferon responses via SDH inhibition–induced mtRNA release and through PRDX5-dependent mitochondrial ROS–cGAS–STING1 activation, highlighting its context-dependent dual roles in immune regulation.
Credit
Yingyi Yang from UT Southwestern Medical Center, USA Image Source Link: https://doi.org/10.1016/j.jointm.2025.10.002
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