| First Author | Yin A | Year | 2021 |
| Journal | Clin Exp Immunol | Volume | 203 |
| Issue | 3 | Pages | 433-447 |
| PubMed ID | 33232517 | Mgi Jnum | J:345529 |
| Mgi Id | MGI:7595958 | Doi | 10.1111/cei.13555 |
| Citation | Yin A, et al. (2021) FAM96A knock-out promotes alternative macrophage polarization and protects mice against sepsis. Clin Exp Immunol 203(3):433-447 |
| abstractText | 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. |
