Engagement of the Fc epsilon RI stimulates the production of IL-16 in Langerhans cell-like dendritic cells.
Preferential uptake and presentation of IgE-bound allergens by epidermal Langerhans cells (LC) via the high affinity IgE receptor, FcepsilonRI, is regarded as an important mechanism in the induction of cutaneous inflammation in atopic dermatitis. Here, we show that activation of monocyte-derived LC-like dendritic cells (LLDC) through engagement of FcepsilonRI induces the expression of IL-16, a chemoattractant factor for dendritic cells, CD4+ T cells, and eosinophils. We found that ligation of FcepsilonRI on LLDC derived from atopic dermatitis patients that express high levels of FcepsilonRI increases IL-16 mRNA expression and storage of intracellular IL-16 protein and enhances the secretion of mature IL-16 in a biphasic manner. An early release of IL-16 (peak at 4 h) is independent of protein synthesis, while a more delayed release (peak at 12 h) requires protein synthesis and occurs subsequent to the induction of IL-16 mRNA and intracellular accumulation of pro-IL-16. There was evidence that LLDC use caspase-1 to process IL-16, as inhibition of caspase-1, but not of caspase-3, partially prevented the release of IL-16 in response to ligation of FcepsilonRI. In an in vivo model of IgE-dependent LC activation, the atopy patch test, positive skin reactions were also associated with the induction of IL-16 in epidermal dendritic cells. These data indicate that IL-16 released from LC after allergen-mediated activation through FcepsilonRI may link IgE-driven and cellular inflammatory responses in diseases such as atopic dermatitis.
Reich
K
K
Department of Dermatology, Georg- August-University, Göttingen, Germany. kreich@gwdg.de
Heine
A
A
Hugo
S
S
Blaschke
V
V
Middel
P
P
Kaser
A
A
Tilg
H
H
Blaschke
S
S
Gutgesell
C
C
Neumann
C
C
D020170:Caspase 1 / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D019410:Interleukin-16 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010328:Patch Tests; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism / Q000502:physiology; D017455:Receptors, IgE / Q000378:metabolism* / Q000502:physiology
D019410:Interleukin-16; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; D007073:Immunoglobulin E; D020170:Caspase 1