Oligosaccharide modification by N ‐acetylglucosaminyltransferase‐ V in macrophages are involved in pathogenesis of bleomycin‐induced scleroderma

Oligosaccharide modification by N ‐acetylglucosaminyltransferase‐ V ( G n T ‐ V ), which catalyses the formation of β 1,6 G lc NA c ( N ‐acetylglucosamine) branches on N ‐glycans, is associated with various pathologies, such as cancer metastasis, multiple sclerosis and liver fibrosis. In this study, we demonstrated the involvement of G n T ‐ V in the pathophysiology of scleroderma. High expression of G n T ‐ V was observed in infiltrating cells in skin section samples from systemic and localized patients with scleroderma. Most of the infiltrating cells were T cells and macrophages, most of which were CD 163 + M 2 macrophages. To determine the role of G n T ‐ V in scleroderma, we next investigated skin sclerosis in G n T ‐ V knockout ( MGAT 5 −/− ) mice. Expression of G n T ‐ V was also elevated in bleomycin ( BLM )‐injected sclerotic skin, and MGAT 5 −/− mice were resistant to BLM ‐induced skin sclerosis with reduced collagen type 1 α 1 content, suggesting the biological significance of G n T ‐ V in skin sclerosis. Furthermore, the number of CD 163 + M 2 macrophages and CD 3‐positive T cells in BLM ‐induced skin sclerosis was significantly fewer in MGAT 5 −/− mice. In bone marrow‐derived macrophages ( BMDM s), IL ‐4‐induced expressions of F izz1 and Y m1 were significantly reduced in MGAT 5 −/− mice‐derived BMDM s. Taken together, these results suggest the induction of G n T ‐ V in skin sclerosis progression is possibly dependent on increased numbers of M 2 macrophages in the skin, which are important for tissue fibrosis and remodelling.