| First Author | Kidder D | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 6 | Pages | 2593-602 |
| PubMed ID | 23408841 | Mgi Jnum | J:193817 |
| Mgi Id | MGI:5469747 | Doi | 10.4049/jimmunol.1201172 |
| Citation | Kidder D, et al. (2013) Sialoadhesin Ligand Expression Identifies a Subset of CD4+Foxp3- T Cells with a Distinct Activation and Glycosylation Profile. J Immunol 190(6):2593-602 |
| abstractText | 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 CD4Foxp3 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 approximately 20% CD4Foxp3 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 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 alpha2,3-sialylation in SnL expression was demonstrated by increased binding of alpha2,3-linkage-specific Maackia amurensis lectin, increased expression of alpha2,3-sialyltransferase ST3GalVI, and loss of SnL following treatment with an alpha2,3-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 CD4Foxp3 Teffs was also observed in vivo using the New Zealand Black x 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. |
