Deficiency of P2RY11 causes narcolepsy and attenuates the recruitment of neutrophils and macrophages in the inflammatory response in zebrafish.

Autor: Zhao L; Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China., Wang LF; Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China., Wang YC; Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China., Liu A; Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China., Xiao QW; Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China., Hu MC; Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China., Sun MZ; Institute of Robotics and Automatic Information System (IRAIS), Tianjin Key Laboratory of Intelligent Robotic (tjKLIR), Nankai University, Tianjin, 300350, China., Hao HY; Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China., Gao Q; Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China., Zhao X; Institute of Robotics and Automatic Information System (IRAIS), Tianjin Key Laboratory of Intelligent Robotic (tjKLIR), Nankai University, Tianjin, 300350, China. zhaoxin@nankai.edu.cn., Chen DY; Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China. chendy@nankai.edu.cn.
Jazyk: angličtina
Zdroj: Cell biology and toxicology [Cell Biol Toxicol] 2024 May 21; Vol. 40 (1), pp. 36. Date of Electronic Publication: 2024 May 21.
DOI: 10.1007/s10565-024-09882-5
Abstrakt: Purinergic receptor P2Y11, a G protein-coupled receptor that is stimulated by extracellular ATP, has been demonstrated to be related to the chemotaxis of granulocytes, apoptosis of neutrophils, and secretion of cytokines in vitro. P2Y11 mutations were associated with narcolepsy. However, little is known about the roles of P2RY11 in the occurrence of narcolepsy and inflammatory response in vivo. In this study, we generated a zebrafish P2Y11 mutant using CRISPR/Cas9 genome editing and demonstrated that the P2Y11 mutant replicated the narcolepsy-like features including reduced HCRT expression and excessive daytime sleepiness, suggesting that P2Y11 is essential for HCRT expression. Furthermore, we accessed the cytokine expression in the mutant and revealed that the P2RY11 mutation disrupted the systemic inflammatory balance by reducing il4, il10 and tgfb, and increasing il6, tnfa, and il1b. In addition, the P2RY11-deficient larvae with caudal fin injuries exhibited significantly slower migration and less recruitment of neutrophils and macrophages at damaged site, and lower expression of anti-inflammatory cytokines during tissue damage. All these findings highlight the vital roles of P2RY11 in maintaining HCRT production and secreting anti-inflammatory cytokines in the native environment, and suggested that P2RY11-deficient zebrafish can serve as a reliable and unique model to further explore narcolepsy and inflammatory-related diseases with impaired neutrophil and macrophage responses.
(© 2024. The Author(s).)
Databáze: MEDLINE
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