TRIM16 Inhibits Inflammation by Interacting With and Ubiquitinating TRAF2 in a Colitis Model

作者：Dongliang Li, Li Zhou, Bo Zhang, Shuai Wang, Qingyu Liang, Qiuhua Liu, Chen‐Jiang Qu, Liang Ji · 发表于：Journal of Cellular and Molecular Medicine · 年份：2025 · DOI：10.1111/jcmm.70917 · 被引用次数：2 · 研究领域：interferon and immune responses、Inflammasome and immune disorders、Immune Response and Inflammation

Tripartite motif 16 (TRIM16), an E3 ubiquitin ligase, plays crucial roles in regulating cell proliferation, differentiation, autophagy and immunity. Several studies have suggested that TRIM16 may function as an anti-inflammatory factor in various diseases. However, the functional significance and regulatory mechanisms of TRIM16 in inflammatory bowel disease (IBD) have yet to be fully explored. This investigation examined the expression and underlying mechanisms of TRIM16 in both in vivo and in vitro models of inflammation. The expression of TRIM16 was significantly decreased in a dextran sulfate sodium (DSS)-induced mouse colitis model and in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Additionally, TRIM16 knockdown in LPS-treated RAW264.7 cells resulted in increased mRNA levels of iNOS, TNF-α and IL-6, as well as in increased activation of the NF-ĸB signalling pathway. Mechanistically, TRIM16 interacted with tumour necrosis factor receptor-associated factor 2 (TRAF2), facilitating its ubiquitination, which in turn impeded NF-ĸB signalling and reduced the expression of inflammatory mediators such as IL-6. Our in vitro and in vivo findings highlight the critical role of TRIM16 in modulating the TRAF2/NF-ĸB signalling pathway. Furthermore, the observed downregulation of TRIM16 was correlated with the onset of colitis, suggesting that TRIM16 may serve as a promising therapeutic target for both the prevention and treatment of this condition.