The Thomsen-Friedenreich antigen-binding lectin jacalin interacts with desmoglein-1 and abrogates the pathogenicity of pemphigus foliaceus autoantibodies in vivo.
Pemphigus foliaceus (PF) is an autoimmune skin blistering disease mediated by pathogenic autoantibodies against the desmosomal core glycoprotein desmoglein-1 (Dsg1). This study demonstrated that the O-glycan-specific plant lectin jacalin binds Dsg1 and inhibits the interaction of Dsg1/PF IgG. N-glycosylation is not involved in the interaction of Dsg1/jacalin or Dsg1/PF IgG. Subcutaneous injection of jacalin into neonatal mice drastically reduced PF IgG deposition at the epidermal cell surface and blocked PF IgG-induced skin blisters, both clinically and histologically. Interestingly, another plant lectin, peanut agglutinin, which shares the same carbohydrate specificity toward the O-linked carbohydrate structure known as Thomsen-Friedenreich antigen (TF antigen, Galβ1-3GalNAcα-O-Ser/Thr), also bound Dsg1 and blocked the skin blistering. In contrast, the plant lectin vicia villosa-B4 (VVL-B4), which shares the carbohydrate specificity toward the O-linked monosaccharide known as Thomsen-nouveau antigen (GalNAc-α1-O-Ser/Thr), did not bind Dsg1 and did not show a protective effect against the disease induced by the autoantibodies. Collectively, these results suggest that the binding of jacalin to O-linked TF carbohydrate motifs on Dsg1 impairs the Dsg1/PF autoantibody interactions and abrogates its pathogenicity in vivo. TF-specific binding ligands may have a potential therapeutic value for PF.
Li
Ning
N
Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. lining@med.unc.edu
Park
Moonhee
M
Zhao
Minglang
M
Hilario-Vargas
Julio
J
McInnes
David M
DM
Prisayanh
Phillip S
PS
Liu
Zhi
Z
Diaz
Luis A
LA
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000937:Antigen-Antibody Reactions / Q000187:drug effects / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology / Q000378:metabolism*; D001323:Autoantibodies / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051183:Desmoglein 1 / Q000276:immunology / Q000378:metabolism*; D004817:Epidermis / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010392:Pemphigus / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D037121:Plant Lectins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D015295:Antigens, Tumor-Associated, Carbohydrate; D001323:Autoantibodies; C495297:DSG1 protein, human; D051183:Desmoglein 1; D037121:Plant Lectins; C043696:jacalin; C016467:Thomsen-Friedenreich antigen