FcepsilonRI-FcgammaRII coaggregation inhibits IL-16 production from human Langerhans-like dendritic cells.
Langerhans-like dendritic cells (LLDC) express the high-affinity IgE receptor FcepsilonRI form that lacks the beta-chain, and may play an important role in allergic inflammation via production of IL-16. Secretion of mediators by human mast cells and basophils is mediated through FcepsilonRI and is decreased by coaggregating these receptors to the low-affinity IgG receptor, FcgammaRII. We used a recently described human Ig fusion protein (GE2), which is composed of key portions of the human gamma1 and the human epsilon heavy chains, to investigate its ability to inhibit IL-16 production from FcepsilonRI-positive Langerhans-like dendritic cells through coaggregation of FcgammaRII and FcepsilonRI. Unstimulated LLDC-derived from CD14-positive monocytes from atopic donors were shown to express FcgammaRII, an ITIM-containing receptor, but not FcepsilonRI or FcgammaRIII which are activating (ITAM) receptors. When passively sensitized with antigen-specific, human IgE and then challenged with antigen, LLDC were stimulated to produce IL-16. However, when FcepsilonRI and FcgammaRII were coaggregated with GE2, IL-16 production was significantly inhibited. Exposure of LLDCs to GE2 alone did not induce IL-16 production. Our results further extend our studies demonstrating the ability of GE2 to inhibit FcepsilonRI-mediated responses through coaggregation with FcgammaRIIB and at the same time show that human LDCC can be modulated in a fashion similar to mast cells and basophils.
Kepley
Christopher L
CL
Department of Internal Medicine, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA, USA. clkepley@mail1.veu.edu
Zhang
Ke
K
Zhu
Daocheng
D
Saxon
Andrew
A
D002478:Cells, Cultured; D006801:Humans; D019410:Interleukin-16 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D011940:Receptor Aggregation / Q000502:physiology; D017455:Receptors, IgE / Q000096:biosynthesis / Q000276:immunology*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction
C445323:FCGR2A protein, human; C499173:FCGR2B protein, human; D019410:Interleukin-16; D017455:Receptors, IgE; D017452:Receptors, IgG