title: Sialoadhesin ligand expression identifies a subset of CD4+Foxp3- T cells with a distinct activation and glycosylation profile.
abstract: 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 ~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-γ 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 α2,3-sialylation in SnL expression was demonstrated by increased binding of α2,3-linkage-specific Maackia amurensis lectin, increased expression of α2,3-sialyltransferase ST3GalVI, and loss of SnL following treatment with an α2,3-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 × 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.
authors: Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom;
authors: Dana
authors: D
authors: Kidder
authors: Hannah E
authors: HE
authors: Richards
authors: Hermann J
authors: HJ
authors: Ziltener
authors: Oliver A
authors: OA
authors: Garden
authors: Paul R
authors: PR
authors: Crocker
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016466:CHO Cells; D002450:Cell Communication / Q000276:immunology; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D006224:Cricetinae; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D006031:Glycosylation; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000096:biosynthesis* / Q000172:deficiency
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008024:Ligands; D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse