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FAM96A knock-out promotes alternative macrophage polarization and protects mice against sepsis
- Source :
- Clin Exp Immunol
- Publication Year :
- 2020
- Publisher :
- Oxford University Press (OUP), 2020.
-
Abstract
- Summary Sepsis is an intractable clinical syndrome characterized by organ dysfunction when the body over-responds to an infection. Sepsis has a high fatality rate and lacks effective treatment. Family with sequence similarity 96 member A (FAM96A) is an evolutionarily conserved protein with high expression in the immune system and is related to cytosolic iron assembly and tumour suppression; however, research has been rarely conducted on its immune functions. Our study found that Fam96a−/− mice significantly resisted lesions during sepsis simulated by caecal ligation and puncture (CLP) or endotoxicosis models. After a challenge with lipopolysaccharide (LPS) or infection, Fam96a−/− mice exhibited less organ damage, longer survival and better bacterial clearance with decreased levels of proinflammatory cytokines. While screening several subsets of immune cells, FAM96A-expressing macrophages as the key cell type inhibited sepsis development. In-vivo macrophage depletion or adoptive transfer experiments abrogated significant differences in the survival of sepsis between Fam96a−/− and wild-type mice. Results of the bone marrow-derived macrophage (BMDM) polarization experiment indicated that FAM96A deficiency promotes the transformation of uncommitted monocytes/macrophages (M0) into M2 macrophages, secreting fewer proinflammatory cytokines. FAM96A may mediate an immunometabolism shift – from oxidative phosphorylation (OXPHOS) to glycolysis – in macrophages during sepsis, mirrored by reactive oxygen species (ROS) and glucose uptake. These data demonstrate that FAM96A regulates inflammatory response and provide a novel genomic insight for sepsis treatment.
- Subjects :
- Lipopolysaccharides
0301 basic medicine
Lipopolysaccharide
Multiple Organ Failure
Immunology
Macrophage polarization
Inflammation
Cell Line
Proinflammatory cytokine
Sepsis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Immune system
medicine
Animals
Immunology and Allergy
Macrophage
Mice, Knockout
business.industry
Macrophages
Organ dysfunction
Original Articles
Macrophage Activation
medicine.disease
Survival Analysis
Endotoxemia
Mice, Inbred C57BL
030104 developmental biology
chemistry
Cytokines
Inflammation Mediators
medicine.symptom
Carrier Proteins
Reactive Oxygen Species
business
030215 immunology
Subjects
Details
- ISSN :
- 13652249 and 00099104
- Volume :
- 203
- Database :
- OpenAIRE
- Journal :
- Clinical and Experimental Immunology
- Accession number :
- edsair.doi.dedup.....0b591f645ba796ca13414f83c7e92da7
- Full Text :
- https://doi.org/10.1111/cei.13555