Neutrophil extracellular traps license macrophage production of chemokines to facilitate CD8+ T cell infiltration in obstruction-induced renal fibrosis
Rattachement africain : cn, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Renal fibrosis is a common mechanism leading to kidney failure in chronic kidney diseases (CKDs), including obstructive nephropathy (ON). Dysregulated inflammation is central to the development of renal fibrosis, but how local immune cells within the tissue microenvironment integrate and coordinate to drive this condition remains largely unknown. Herein, we documented that neutrophils were abundantly recruited and expelled neutrophil extracellular traps (NETs) in human and mouse fibrotic kidneys. Importantly, circulating levels of NET components displayed a significant correlation with worsened kidney function in ON patients. In the unilateral ureteral obstruction (UUO) mouse model, blocking NETs by protein-arginine deiminase type 4 (PAD4) deletion or DNase treatment significantly impaired NET formation and inhibited renal fibrosis and inflammation, whereas NET adoptive transfer exacerbated the fibrotic process. Moreover, NET-mediated renal fibrosis was associated with enhanced infiltration of cytotoxic CD8+ T cells, which produced granzyme B (GZMB) to drive tubular cell epithelial-mesenchymal transition (EMT) and fibroblast activation. Accordingly, pharmacological inhibition of GZMB resulted in blunted kidney inflammation and fibrosis. Furthermore, NETs profoundly potentiated the production of T-cell chemokines CXCL9/10/11 in macrophages, but not in tubular cells or fibroblasts, thus driving T-cell infiltration and fueling inflammatory cascades in the kidneys. Mechanistically, the NET-macrophage interaction was partially mediated by the TLR2/4 signaling. Thus, our work reveals a previously unexplored role of the collaboration between NETs and macrophages in supporting CD8+ T cell infiltration, which orchestrates kidney inflammation and fibrosis.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Neutrophil extracellular traps license macrophage production of chemokines to facilitate CD8+ T cell infiltration in obstruction-induced renal fibrosis
- Date Crossref
- 25/02/2025
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Beijing University of Chinese Medicine pays non établi dans la noticeUniversité ou école supérieure
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Chinese PLA General Hospital Department of Pediatric Urology pays non établi dans la noticeÉtablissement de santé
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PLA Academy of Military Science pays non établi dans la noticeStructure de recherche
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National Center on Birth Defects and Developmental Disabilities pays non établi dans la noticeStructure de recherche
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The People's Hospital of Guangxi Zhuang Autonomous Region pays non établi dans la noticeÉtablissement de santé
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Nanxi Mountain Hospital pays non établi dans la noticeÉtablissement de santé
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Sichuan Mianyang 404 Hospital pays non établi dans la noticeÉtablissement de santé
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Medical School of Chinese PLA pays non établi dans la noticeUniversité ou école supérieure
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National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology pays non établi dans la noticeStructure de recherche
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The PLA Rocket Force Characteristic Medical Center pays non établi dans la noticeÉtablissement de santé
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Nanxishan Hospital of Guangxi Zhuang Autonomous Region pays non établi dans la noticeÉtablissement de santé
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Nanxi Shan Hospital of Guangxi Zhuang Autonomous Region pays non établi dans la noticeÉtablissement de santé
Beijing University of Chinese Medicine, Department of Pediatric Urology — Chinese PLA General Hospital et PLA Academy of Military Science, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.