title: Human immature dendritic cells efficiently bind and take up secretory IgA without the induction of maturation.
abstract: Immature dendritic cells (DC) reside in peripheral tissues, where they pick up and process incoming pathogens via scavenger receptors or FcR such as FcgammaR and FcepsilonR. At mucosal surfaces, IgA is the main Ig to protect the body from incoming pathogens. In addition, DC are present in high numbers at these sites. We detected expression of FcalphaR (CD89) on the CD14+ population of CD34+ progenitor-derived DC and on monocyte-derived DC (MoDC). However, CD89 expression was strongly decreased upon differentiation from monocyte to DC. We found only minimal binding of serum IgA to MoDC but strong binding of secretory IgA (SIgA). The SIgA binding to MoDC could not be blocked by anti-CD89 blocking Abs. DC efficiently internalized SIgA, but not serum IgA, and uptake of SIgA could be blocked by specific sugars or partially by Ab reactive with mannose receptor. Importantly, binding and uptake of SIgA was not accompanied by signs of DC maturation, such as increased expression of CD86 and CD83 or induction of cytokine secretion. These data indicate that SIgA can interact with DC not via CD89, but via carbohydrate-recognizing receptors like mannose receptor and suggest that uptake of SIgA-containing immune complexes by immature DC may be a mechanism to modulate mucosal immune responses.
authors.affiliation: Department of Cell Biology and Histology, University of Amsterdam, Amsterdam Medical Center, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands. h.c.heystek@amc.uva.nl
authors.forename: Heleen C
authors.initials: HC
authors.lastname: Heystek
authors.forename: Corinne
authors.initials: C
authors.lastname: Moulon
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Woltman
authors.forename: Pierre
authors.initials: P
authors.lastname: Garonne
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004705:Endocytosis; D005434:Flow Cytometry; D006801:Humans; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009000:Monocytes / Q000276:immunology; D009005:Monosaccharides / Q000494:pharmacology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology / Q000502:physiology; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D020298:U937 Cells
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D018952:Antigens, CD34; D016207:Cytokines; C036832:Fc(alpha) receptor; D007071:Immunoglobulin A, Secretory; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009005:Monosaccharides; D011956:Receptors, Cell Surface; D011961:Receptors, Fc