A subset of human dendritic cells expresses IgA Fc receptor (CD89), which mediates internalization and activation upon cross-linking by IgA complexes

Immature dendritic cells (DC) sample Ags within nonlymphoid tissues and acq uire exogenous proteins/pathogens via scavenger receptors or Ig FcR such as Fc gammaR and Fc epsilonR, IgA is present in a significant proportion amon g serum Ig and is the main isotype in mucosae, where DC are numerous. We fo und that a functional Fc alphaR (CD89) was expressed in situ and in vitro o n interstitial-type DC but not on Langerhans cell-type DC. Interstitial-typ e DC expressed CD89 as a 50- to 75-kDa glycoprotein with a 32-kDa protein c ore, which was down-regulated upon addition of TGF-beta1, DC, Fc alphaR spe cifically, bound IgA1 and IgA2, Cross-linking of CD89 on DC triggered endoc ytosis in time-dependent manner. In addition, internalization of polymeric IgA complexes induced the production of IL-10 and DC activation, as reflect ed by up-regulation of CD86 costimulatory molecules, class II MHC expressio n, and increased allostimulatory activity. Therefore, interstitial-type DC may use Fc alphaR-mediated Ag sampling in the subepithelium to check tissue integrity while Langerhans cells inside epithelial layers may neglect IgA immune complexes.