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Published online before print September 15, 2004
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*INSERM E0225, Bichat Medical School, Paris, France; and
CNRS UMR8147, Necker Hospital, Paris, France
@ To whom correspondence should be addressed. E-mail: MONTEIRO{at}BICHAT.INSERM.FR.
| Abstract |
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Dendritic cells (DC) are the most efficient antigen-presenting cells residing in mainly peripheral tissues. Antigen uptake by DC is particularly efficient, being mediated by various receptors such as lectin, scavenger receptors, and Fc receptors (FcRs). Immunoglobulin A (IgA) is part of the first-line immune barrier in mucosae, where DC are numerous. A member of the FcR family, Fc
RI, is expressed on interstitial DC. We report here that monocyte-derived DC (Mo-DC) express another IgA receptor (IgA-R), the transferrin receptor (TfR), even in the absence of DC proliferation in vitro. Upon incubation with inflammatory cytokines such as tumor necrosis factor
and interleukin (IL)-1
or maturating agents (lipopolysaccharide, CD40 ligand), Fc
RI and TfR expression on Mo-DC was specifically up-regulated, whereas Fc
Rs and Fc
RI expression was down-regulated. IgA-Rs were functional, being able to mediate endocytosis by immature and activated Mo-DC. Although Fc
RI internalized IgA complexes on both types of DC, TfR was only able to mediate IgA complex internalization by immature cells. Cross-linking of Fc
RI but not of TfR resulted in up-regulation of major histocompatibility complex (MHC) class II/CD86 expression and secretion of IL-10 and IL-12 by immature Mo-DC. Moreover, in activated Mo-DC, cross-linking of Fc
RI could up-regulated MHC class II/CD86 and triggered IL-10 secretion. Our findings led us to propose that Fc
RI expressed by interstitial-type DC could play a critical role to sample IgA-recognized antigens and also in DC activation.
Key Words: Fc receptor transferrin receptor dendritic cells
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