白细胞介素-40的缺乏通过抑制NETosis来预防实验性坏死性小肠结肠炎的肠道损伤
Deficiency of interleukin-40 prevents intestinal damage in experimental necrotizing enterocolitis by inhibiting NETosis.
摘要(中文译文)
坏死性小肠结肠炎（NEC）是一种影响早产儿的严重炎症性疾病，以肠坏死和全身性炎症为特征。本研究检测了NEC患者中白细胞介素-40（IL-40）的水平，并利用临床样本和实验模型探讨了其对炎症、中性粒细胞功能及中性粒细胞胞外诱捕网（NET）形成的影响。研究获取了诊断为NEC的婴儿及对照受试者的肠道组织样本，随后测定血浆IL-40水平。采用IL-40基因敲除（IL-40−/−）和野生型（WT）小鼠建立实验性NEC模型，以评估IL-40缺失对疾病进展的影响。结果表明，与对照组相比，NEC患者中IL-40水平显著升高，且与NET形成增强及疾病严重程度加重相关。在小鼠模型中，IL-40−/−小鼠表现出NEC严重程度减轻、中性粒细胞浸润减少及NET释放减少。机制研究表明，IL-40的缺失降低了线粒体活性氧（ROS）的产生和氧化线粒体DNA（ox-mtDNA）的释放，二者对NET形成均至关重要。总之，本研究强调了IL-40通过促进中性粒细胞活化和NETosis在NEC中发挥重要作用。靶向IL-40可能通过抑制NETosis和减轻炎症，成为减轻NEC肠道损伤的一种有前景的治疗策略。
Abstract
Necrotizing enterocolitis (NEC) is a severe inflammatory condition that affects premature infants, marked by intestinal necrosis and systemic inflammation. This study examined interleukin-40 (IL-40) levels in patients with NEC and investigated its influence on inflammation, neutrophil function, and the formation of neutrophil extracellular traps (NET) using clinical samples and experimental models. Intestinal tissue samples were obtained from infants diagnosed with NEC and from control subjects, with plasma IL-40 levels subsequently measured. An experimental NEC model was established employing IL-40 knockout (IL-40−/−) and wild-type (WT) mice to assess the effects of IL-40 deficiency on disease progression. Results indicated that IL-40 levels were significantly elevated in NEC patients compared to controls, correlating with enhanced NET formation and greater disease severity. In the murine model, IL-40−/− mice demonstrated reduced NEC severity, lower neutrophil infiltration, and diminished NET release. Mechanistic studies indicated that the absence of IL-40 decreased mitochondrial reactive oxygen species (ROS) production and the release of oxidized mitochondrial DNA (ox-mtDNA), both crucial for NET formation. In conclusion, this study highlights the significant role of IL-40 in NEC by promoting neutrophil activation and NETosis. Targeting IL-40 may present a promising therapeutic approach to mitigate intestinal damage in NEC by inhibiting NETosis and reducing inflammation.
如何引用
AMA
Yunfei Zhang, Cuilian Ye, Xin Zhong, Xionghui Ding, Yihang Yang, Yue Ma, et al. Deficiency of interleukin-40 prevents intestinal damage in experimental necrotizing enterocolitis by inhibiting NETosis.. Cell communication and signaling : CCS. 2026; doi:10.1186/s12964-026-02769-4.
APA
Yunfei Zhang, Cuilian Ye, Xin Zhong, Xionghui Ding, Yihang Yang, Yue Ma, et al (2026). Deficiency of interleukin-40 prevents intestinal damage in experimental necrotizing enterocolitis by inhibiting NETosis.. Cell communication and signaling : CCS. https://doi.org/10.1186/s12964-026-02769-4
GB/T 7714
Yunfei Zhang, Cuilian Ye, Xin Zhong, Xionghui Ding, Yihang Yang, Yue Ma, et al. Deficiency of interleukin-40 prevents intestinal damage in experimental necrotizing enterocolitis by inhibiting NETosis.[J]. Cell communication and signaling : CCS, 2026 doi:10.1186/s12964-026-02769-4.
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