FAM96A knockout promotes alternative macrophage polarisation and protects mice against sepsis.

FAM96A knockout promotes alternative macrophage polarisation and protects mice against sepsis. Clin Exp Immunol. 2020 Nov 24;: Authors: Yin A, Chen W, Cao L, Li Q, Zhu X, Wang L Abstract Sepsis is an intractable clinical syndrome characterised 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. Result of the bone-marrow-derived macrophage (BMDM) polarisation experiment indicated that FAM96A deficiency promotes the transformation of uncommitted monocytes/mac...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research