Unexpected functions of FcepsilonRI on antigen-presenting cells.
In contrast to mast cells and basophils, the high affinity IgE receptor (FcepsilonRI) on antigen-presenting cells (APC) shows structural and functional differences. It consists only of a minimal structure of one alpha- and two gamma-chains and enables APC to efficiently take up and present antigen in IgE-mediated delayed-type hypersensitivity reactions that are thought to play a pivotal role in atopic diseases. However, recent studies of FcepsilonRI signal transduction and function on APC suggest additional mechanisms by which FcepsilonRI engagement on APC could affect inflammatory reactions. FcepsilonRI ligation is able to induce major signaling events like protein tyrosine kinase activation including p72(syk) leading to PLC-gamma1 phosphorylation and consecutive calcium influx. Late signaling events like the activation of transcription factors such as NF-kappaB provide a link to the release of proinflammatory cytokines and chemokines, Th-polarizing factors such as IL-12 and the induction of antiapoptotic factors. FcepsilonRI-mediated IL-10 production in monocytes could also influence their differentiation. Since there are hints that in vivo a functional FcepsilonRI signaling pathway only exists in individuals from an atopic background, we suggest that these unexpected mechanisms may have an effect on inflammatory reactions in atopic diseases.
Kraft
S
S
Department of Dermatology, Friedrich Wilhelms University, Bonn, Germany.
Katoh
N
N
Novak
N
N
Koch
S
S
Bieber
T
T
D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D017209:Apoptosis; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D017455:Receptors, IgE / Q000502:physiology*; D015398:Signal Transduction
D016207:Cytokines; D016328:NF-kappa B; D017455:Receptors, IgE