title: The S. mansoni glycoprotein ω-1 induces Foxp3 expression in NOD mouse CD4⁺ T cells.
abstract: Immunization with Schistosoma mansoni soluble antigen preparations protects non-obese diabetic (NOD) mice against the development of type 1 diabetes. These preparations have long been known to induce Th2 responses in vitro and in vivo. Recently, two separate groups have reported that ω-1, a well-characterized glycoprotein in S. mansoni soluble egg antigens (SEA), which with IL-4 inducing principle of S. mansoni eggs (IPSE/α-1) is one of the two major glycoproteins secreted by live eggs, is a major SEA component responsible for this effect. We found that ω-1 induces Foxp3 as well as IL-4 expression when injected in vivo. We confirmed that ω-1 conditions DCs to drive Th2 responses and further demonstrated that ω-1 induces Foxp3(+)  T cells from NOD mouse naïve T cells. In contrast, IPSE/α-1 did not drive Foxp3 responses. The in vitro development of Foxp3-expressing T cells by ω-1 was TGF-β- and retinoic acid-dependent. Our work, therefore, identifies ω-1 as an important factor for the induction of Foxp3(+)  T cells by SEA in NOD mice.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, UK. pz206@cam.ac.uk
authors.forename: Paola
authors.initials: P
authors.lastname: Zaccone
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Burton
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gibbs
authors.forename: Nigel
authors.initials: N
authors.lastname: Miller
authors.forename: Frances M
authors.initials: FM
authors.lastname: Jones
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schramm
authors.forename: Helmut
authors.initials: H
authors.lastname: Haas
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Doenhoff
authors.forename: David W
authors.initials: DW
authors.lastname: Dunne
authors.forename: Anne
authors.initials: A
authors.lastname: Cooke
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control; D004527:Egg Proteins / Q000008:administration & dosage; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015801:Helminth Proteins / Q000008:administration & dosage; D007114:Immunization; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D012550:Schistosoma mansoni / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism
chemical_list: D004527:Egg Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015801:Helminth Proteins; C474807:IPSE protein, Schistosoma mansoni; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D014212:Tretinoin