Glycan Activation of Clec4b Induces Reactive Oxygen Species Protecting against Neutrophilia and Arthritis

• DOI: 10.3390/antiox11010012
• Publication Date: 2021-12-22T15:24:52Z
• Authors: Mike Aoun; Xiaojie Cai; Bingze Xu; Gonzalo Fernandez...; Michael Yi Bonner; Yibo He; Liselotte Bäckdahl; Rikard Holmdahl
• Keywords: Neutrophilia; Respiratory burst

Animal models for complex diseases are needed to position and analyze the function of interacting genes. Previous positional cloning identified Ncf1 Clec4b be major regulators arthritis in rats. Here, we investigate epistasis between Clec4b, two We find that exert an additive effect on given by their joint ability regulate neutrophils. Both genes highly expressed neutrophils, together regulating neutrophil availability capacity generate reactive oxygen species. Using a glycan array, identify key ligands demonstrate Clec4b-specific stimulation triggers neutrophils into oxidative burst. Our observations highlight as important regulator how epistatic interactions affect susceptibility to, severity of, autoimmune arthritis.