Cheng Wenyue, Li Fan, Zhang Yuan, Gao Yunhuan, Yang Rongcun
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China.
Translational Medicine Institute, Tianjin Union Medical Center of Nankai University, Tianjin, China.
Front Immunol. 2025 Aug 26;16:1642783. doi: 10.3389/fimmu.2025.1642783. eCollection 2025.
The functional state of macrophages is regulated by multiple factors and closely related to the occurrence and development of various diseases. The aim of this study is to discover a new regulatory factor in macrophages, which can serve as a target for disease prevention and treatment.
Long non-coding RNA (lncRNA) lncOlfr29 was discovered through RNA sequencing. The functions of lncOlfr29 were investigated by bioinformatics analysis, lncOlfr29 shRNA silencing and overexpressing adenovirus, and lncOlfr29 knockout (KO) mice. To investigate the function of lncOlfr29 , we also established a Salmonella infection model and DSS-mediated colitis using lncOlfr29 KO mice.
We here identified a novel lncRNA named lncOlfr29 in macrophages and demonstrated that lncOlfr29 promoted inflammation by enhancing NLRP3-mediated IL-1 β maturation and pyroptosis of macrophages. experiments showed that lncOlfr29 could promote resistance to Salmonella infection and sensitivity to DSS mediated colitis. Mechanistically, lncOlfr29 could bind to zinc finger protein 36 (ZFP36) to eliminate the degradation of ZFP36 on NLRP3 mRNA. Knockout of lncOlfr29 led to a decrease of NLRP3 in cytoplasm, reducing macrophage pyroptosis and IL-1 β maturation.
Our data demonstrate that lncOlfr29 can regulate expression of NLRP3 through binding with ZFP36. These results will provide new insights into the treatment of inflammatory diseases.
巨噬细胞的功能状态受多种因素调节，且与多种疾病的发生发展密切相关。本研究旨在发现巨噬细胞中的一种新的调节因子，可为疾病防治提供靶点。
通过RNA测序发现长链非编码RNA（lncRNA）lncOlfr29。采用生物信息学分析、lncOlfr29短发夹RNA（shRNA）沉默、过表达腺病毒以及lncOlfr29基因敲除（KO）小鼠等方法研究lncOlfr29的功能。为研究lncOlfr29的功能，我们还利用lncOlfr29 KO小鼠建立了沙门氏菌感染模型和葡聚糖硫酸钠（DSS）介导的结肠炎模型。
我们在巨噬细胞中鉴定出一种名为lncOlfr29的新型lncRNA，并证明lncOlfr29通过增强NLRP3介导的白细胞介素-1β（IL-1β）成熟和巨噬细胞焦亡来促进炎症。实验表明，lncOlfr29可促进对沙门氏菌感染的抵抗力以及对DSS介导的结肠炎的敏感性。机制上，lncOlfr29可与锌指蛋白36（ZFP36）结合，消除ZFP36对NLRP3 mRNA的降解作用。lncOlfr29基因敲除导致细胞质中NLRP3减少，降低巨噬细胞焦亡和IL-1β成熟。
我们的数据表明，lncOlfr29可通过与ZFP36结合来调节NLRP3的表达。这些结果将为炎症性疾病的治疗提供新的见解。
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