The role of sulfatase-2 (a heparan sulfate proteoglycan modifying enzyme) in regulating immune function.
The effect of cytokines, chemokines and growth factors on immune cells is fine-tuned by their interactions with heparan sulfate (HS) proteoglycans (PG), which can bind over 400 different proteins. Binding to HS can establish gradients, protect proteins from proteolysis, fine-tune their bioactivity (e. g. by chemokine oligomerization) and influence receptor binding. HSPGs are composed of a core protein that carries one or more linear, covalently-attached HS polysaccharide side chain, consisting of N-acetylglucosamine (GlcNAc) and hexuronic acid disaccharide repeats. These HS side chains are extensively modified by N-, 2-O, 3-O and 6-O sulfation, enabling proteins to bind to HS through their positively charged amino acids (Arg and Lys). 6-O sulfation is the only sulfation pattern that can be post-synthetically fine-tuned by the extracellular sulfatase SULF2 that removes 6-O sulfate groups. This indicates that SULF2 is important for the for the regulation of the bioactivity of mediators that bind to HS. I aimed to study if SULF2 affects inflammation in rheumatoid arthritis and which cell types/ mediators are involved.