近日,美国密歇根大学教授Carole A. Parent及其研究团队报道了中性粒细胞分泌外泌体相关的DNA来解决无菌急性炎症。该项研究成果发表在2025年5月22日出版的《自然—细胞生物学》上。
研究组之前的研究表明,在炎症期间,含有LTB4的外泌体通过核膜衍生的多泡体分泌是中性粒细胞有效浸润所必需的。
在这里,该课题组报道了这些外泌体与核DNA的共同分泌促进了无菌炎症的单核细胞皮肤模型中中性粒细胞浸润的溶解。活化的中性粒细胞在定向迁移时表现出快速和重复的DNA分泌,这是一种不同于自杀性中性粒细胞胞外陷阱释放和细胞死亡的机制。DNA在核膜多泡体管腔内的包装是由核纤层蛋白B受体和染色质去浓缩介导的。这些发现促进了他们对炎症期间中性粒细胞功能和DNA分泌的生理相关性的理解。
研究人员表示,急性炎症以中性粒细胞的快速涌入为特征,是一种保护性反应,如果不加以解决,可导致慢性炎症性疾病。
附:英文原文
Title: Neutrophils secrete exosome-associated DNA to resolve sterile acute inflammation
Author: Arya, Subhash B., Collie, Samuel P., Xu, Yang, Fernandez, Martin, Sexton, Jonathan Z., Mosalaganti, Shyamal, Coulombe, Pierre A., Parent, Carole A.
Issue&Volume: 2025-05-22
Abstract: Acute inflammation, characterized by a rapid influx of neutrophils, is a protective response that can lead to chronic inflammatory diseases when left unresolved. We previously showed that secretion of LTB4-containing exosomes via nuclear envelope-derived multivesicular bodies is required for effective neutrophil infiltration during inflammation. Here we report that the co-secretion of these exosomes with nuclear DNA facilitates the resolution of the neutrophil infiltrate in a mouse skin model of sterile inflammation. Activated neutrophils exhibit rapid and repetitive DNA secretion as they migrate directionally using a mechanism distinct from suicidal neutrophil extracellular trap release and cell death. Packaging of DNA in the lumen of nuclear envelope-multivesicular bodies is mediated by lamin B receptor and chromatin decondensation. These findings advance our understanding of neutrophil functions during inflammation and the physiological relevance of DNA secretion.
DOI: 10.1038/s41556-025-01671-4
Source: https://www.nature.com/articles/s41556-025-01671-4
Nature Cell Biology:《自然—细胞生物学》,创刊于1999年。隶属于施普林格·自然出版集团,最新IF:28.213
官方网址:https://www.nature.com/ncb/
投稿链接:https://mts-ncb.nature.com/cgi-bin/main.plex