气候变化领域集成服务门户(CCPortal): Sema7A is crucial for resolution of severe inflammation

CCPortal

DOI	10.1073/pnas.2017527118
	Sema7A is crucial for resolution of severe inflammation
	Körner A.; Bernard A.; Fitzgerald J.C.; Alarcon-Barrera J.C.; Kostidis S.; Kaussen T.; Giera M.; Mirakaj V.
发表日期	2021
ISSN	00278424
卷号	118 期号:9
英文摘要	Endogenous mediators regulating acute inflammatory responses in both the induction and resolution phases of inflammatory processes are pivotal in host defense and tissue homeostasis. Recent studies have identified neuronal guidance proteins characterized in axonal development that display immunomodulatory functions. Here, we identify the neuroimmune guidance cue Semaphorin 7A (Sema7A), which appears to link macrophage (MΦ) metabolic remodeling to inflammation resolution. Sema7A orchestrated MΦ chemotaxis and chemokinesis, activated MΦ differentiation and polarization toward the proresolving M2 phenotype, and promoted leukocyte clearance. Peritoneal MΦSema7A−/− displayed metabolic reprogramming, characterized by reductions in fatty acid oxidation and oxidative phosphorylation, increases in glycolysis and the pentose phosphate pathway, and truncation of the tricarboxylic acid cycle, which resulted in increased levels of the intermediates succinate and fumarate. The low accumulation of citrate in MΦSema7A−/− correlated with the decreased synthesis of prostaglandins, leading to a reduced impact on lipid-mediator class switching and the generation of specialized pro resolving lipid mediators. Signaling network analysis indicated that Sema7A induced the metabolic reprogramming of MΦ by activating the mTOR- and AKT2-signaling pathways. Administration of Sema7ASL4cd orchestrated the resolution response to tissue homeostasis by shortening the resolution interval, promoting tissue protection in murine peritonitis, and enhancing survival in polymicrobial sepsis. © This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
英文关键词	Inflammation; Lipid mediator; Metabolism; Resolution; Semaphorin 7A
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180443
作者单位	Department of Anesthesiology and Intensive Care Medicine, Molecular Intensive Care Medicine, University Hospital Eberhard-Karls University, Tübingen, 72076, Germany; Hertie Institute for Clinical Brain Research, University Clinic Tübingen, Tübingen, 72076, Germany; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, 2333 ZA, Netherlands; Department of Pediatric Cardiology and Pediatric Intensive Care Medicine, Hannover Medical School, Hannover, 30625, Germany
推荐引用方式 GB/T 7714	Körner A.,Bernard A.,Fitzgerald J.C.,et al. Sema7A is crucial for resolution of severe inflammation[J],2021,118(9).
APA	Körner A..,Bernard A..,Fitzgerald J.C..,Alarcon-Barrera J.C..,Kostidis S..,...&Mirakaj V..(2021).Sema7A is crucial for resolution of severe inflammation.Proceedings of the National Academy of Sciences of the United States of America,118(9).
MLA	Körner A.,et al."Sema7A is crucial for resolution of severe inflammation".Proceedings of the National Academy of Sciences of the United States of America 118.9(2021).