科研之友
微信
新浪微博
Facebook
分享链接
摘要
Sialoadhesin (Sn) is a sialic acid-binding Ig-like lectin expressed selectively on macrophage subsets. In a model of experimental autoimmune encephalomyelitis, Sn interacted with sialylated ligands expressed selectively on CD4(+) Foxp3(+) regulatory T cells (Tregs) and inhibited their proliferation. In this study, we examined the induction of Sn ligands (SnL) on all splenic CD4(+) T cells following in vitro activation. Most CD4(+) Tregs strongly upregulated SnL, whereas only a small subset of similar to 20% CD4(+) Foxp3(-) T cells (effector T cells [Teffs]) upregulated SnL. SnL+ Teffs displayed higher levels of activation markers CD25 and CD69, exhibited increased proliferation, and produced higher amounts of IL-2 and IFN-gamma than corresponding SnL 2 Teffs. Coculture of activated Teffs with Sn+ macrophages or Sn+ Chinese hamster ovary cells resulted in increased cell death, suggesting a regulatory role for Sn-SnL interactions. The key importance of alpha 2,3-sialylation in SnL expression was demonstrated by increased binding of alpha 2,3-linkage-specific Maackia amurensis lectin, increased expression of alpha 2,3-sialyltransferase ST3GalVI, and loss of SnL following treatment with an a2,3-linkage-specific sialidase. The induction of SnL on activated CD4(+) T cells was dependent on N-glycan rather than O-glycan biosynthesis and independent of the mucin-like molecules CD43 and P-selectin glycoprotein ligand-1, previously implicated in Sn interactions. Induction of ligands on CD4(+) Foxp3(-) Teffs was also observed in vivo using the New Zealand Black 3 New Zealand White F1 murine model of spontaneous lupus and SnL levels on Teffs correlated strongly with the degree of proteinuria. Collectively, these data indicate that SnL is a novel marker of activated CD4(+) Teffs that are implicated in the pathogenesis of autoimmune diseases. The Journal of Immunology, 2013, 190: 2593-2602.
- 出版日期2013-3-15
