Duodenal intraepithelial lymphocytes of children with cow milk allergy preferentially bind the glycan-binding protein galectin-3.
A breakdown in intestinal homeostasis results in inflammatory bowel diseases including coeliac disease and allergy. Galectins, evolutionarily conserved beta-galactoside-binding proteins, can modulate immune-epithelial cell interactions by influencing immune cell fate and cytokine secretion. In this study we investigated the glycosylation signature, as well as the regulated expression of galectin-1 and -3 in human duodenal samples of allergic and non-allergic children. Whereas galectin-1 was predominantly localized in the epithelial compartment (epithelial cells and intraepithelial lymphocytes) and the underlying lamina propria (T cells, macrophages and plasma cells), galectin-3 was mainly expressed by crypt epithelial cells and macrophages in the lamina propria. Remarkably, expression of these galectins was not significantly altered in allergic versus non-allergic patients. Investigation of the glycophenotype of the duodenal inflammatory microenvironment revealed substantial alpha2-6-linked sialic acid bound to galactose in lamina propria plasma cells, macrophages and intraepithelial lymphocytes and significant levels of asialo core 1 O-glycans in CD68+ macrophages and enterocytes. Galectin-1 preferentially bound to neutrophils, plasma cells and enterocytes, while galectin-3 binding sites were mainly distributed on macrophages and intraepithelial lymphocytes. Notably, galectin-3, but not galectin-1 binding, was substantially increased in intraepithelial gut lymphocytes of allergic patients compared to non-allergic subjects, suggesting a potential role of galectin-3-glycan interactions in shaping epithelial-immune cell connections during allergic inflammatory processes.
Mercer
N
N
Laboratory of Investigations of the Immune System, Department of Biological Sciences, School of Sciences, University of La Plata, Argentina.
Guzman
L
L
Cueto Rua
E
E
Drut
R
R
Ahmed
H
H
Vasta
G R
GR
Toscano
M A
MA
Rabinovich
G A
GA
Docena
G H
GH
D001665:Binding Sites; D002675:Child, Preschool; D004386:Duodenum / Q000737:chemistry / Q000276:immunology*; D005260:Female; D037483:Galectin 1 / Q000032:analysis / Q000378:metabolism; D037502:Galectin 3 / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D016269:Milk Hypersensitivity / Q000209:etiology / Q000276:immunology*; D019887:Peanut Agglutinin / Q000378:metabolism; D037121:Plant Lectins / Q000378:metabolism; D054788:Ribosome Inactivating Proteins / Q000378:metabolism
D037483:Galectin 1; D037502:Galectin 3; C445499:LGALS1 protein, human; D019887:Peanut Agglutinin; D037121:Plant Lectins; C050600:Sambucus nigra lectins; D054788:Ribosome Inactivating Proteins