A Subset of Human Dendritic Cells Expresses IgA Fc Receptor (CD89), Which Mediates Internalization and Activation Upon Cross-Linking by IgA Complexes

Abstract

Immature dendritic cells (DC) sample Ags within nonlymphoid tissues and acquire exogenous proteins/pathogens via scavenger receptors or Ig FcR such as FcγR and FcεR. IgA is present in a significant proportion among serum Ig and is the main isotype in mucosae, where DC are numerous. We found that a functional FcαR (CD89) was expressed in situ and in vitro on interstitial-type DC but not on Langerhans cell-type DC. Interstitial-type DC expressed CD89 as a 50- to 75-kDa glycoprotein with a 32-kDa protein core, which was down-regulated upon addition of TGF-β1. DC, FcαR specifically, bound IgA1 and IgA2. Cross-linking of CD89 on DC triggered endocytosis in time-dependent manner. In addition, internalization of polymeric IgA complexes induced the production of IL-10 and DC activation, as reflected by up-regulation of CD86 costimulatory molecules, class II MHC expression, and increased allostimulatory activity. Therefore, interstitial-type DC may use FcαR-mediated Ag sampling in the subepithelium to check tissue integrity while Langerhans cells inside epithelial layers may neglect IgA immune complexes.

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

“…An additional property of IgA is its inability to trigger the release of inflammatory mediators through receptors specific for its Fc domain (42)(43)(44). In support of this are two reports showing differential pattern of in vitro-derived DC activation after surface binding of IgA as compared with other Ig isotypes (45,46). This is consistent with the multitask role of protecting against foreign substances and microbes, regulating the commensal microbiota, while at the same time not subjecting the mucosa to undue inflammation (47,48).…”

A Critical Role for Syk Protein Tyrosine Kinase in Fc Receptor-Mediated Antigen Presentation and Induction of Dendritic Cell Maturation

“…Like Fc␥R in mouse DCs, Fc␣R engagement in human DCs induces efficient maturation (33). By contrast, it was recently shown that human monocyte-derived DCs were not induced to mature after Fc␥R engagement (34,35).…”

Human NK cells express Fc receptors for IgA which mediate signal transduction and target cell killing

“…The MR is a marker of alternatively activated cells with enhanced cell function, mediates both pinocytosis and phagocytosis, and serves as a molecular link between innate and adaptive immune response [26]. Because DC efficiently bind sIgA [7] via a receptor with lectin-like properties [25], we were interested to know whether NK cells may bind sIgA via MR. NK cells and monocytes did not bind anti-MR Ab, whereas the MR is highly expressed on monocyte-derived DC [29], as well as on monocyte-derived M ¶ [4]. Furthermore, the percentage of NK (CD3 -CD56 + ) cells binding sIgA did not change when L-fucose, D-galactose, D-glucose, D-mannose or N-acetyl-D-glucosamine were used as inhibitors.…”

“…It has recently been shown that DC express a receptor for IgA [7], and that the binding of IgA occurs via a mannose receptor (MR/CD206) which recognizes carbohydrates patterns [25]. Therefore, we asked whether NK cells constitutively express MR, which may mediate sIgA binding.…”

“…The presence of Fc § R was previously reported on a subpopulation of T and B cells [2], monocytes and macrophages (M ¶ ) [3,4], neutrophils and eosinophils [5,6], and recently on a subset of human DC [7]. On NK cell surface, Fc + RIIIa [8,9], Fc + RIIc [10] and Fc ?…”