Ectosomes from neutrophil‐like cells down‐regulate nickel‐induced dendritic cell maturation and promote Th2 polarization

A new mechanism of dendritic cell modulation by neutrophillike ectosomes in an in vitro model of nickel‐related allergic contact dermatitis. DCs are the first immune cells to be exposed to allergens, including chemical sensitizers, such as nickel, a human TLR4 agonist that induces DC maturation. In...

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Bibliographic Details
Published in:	Journal of leukocyte biology Vol. 97; no. 4; pp. 737 - 749
Main Authors:	Turbica, Isabelle, Gallais, Yann, Gueguen, Claire, Tharinger, Hugo, Al Sabbagh, Chantal, Gorges, Roseline, Gary‐Gouy, He´le`ne, Kerdine‐Ro¨mer, Saadia, Pallardy, Marc, Mascarell, Laurent, Gleizes, Aude, Chollet‐Martin, Sylvie
Format:	Journal Article
Language:	English
Published:	United States 01-04-2015
Subjects:	Allergens - immunology Allergens - pharmacology Antigens, CD - biosynthesis Antigens, CD - genetics B7-H1 Antigen - biosynthesis B7-H1 Antigen - genetics Cell Differentiation Cell-Derived Microparticles - physiology chemical sensitizer Coculture Techniques contact dermatitis Dendritic Cells - drug effects Dendritic Cells - immunology Dermatitis, Allergic Contact - etiology Dermatitis, Allergic Contact - immunology Gene Expression Regulation - immunology HLA-DR Antigens - biosynthesis HLA-DR Antigens - genetics Humans inflammation regulation Leukemia, Myeloid, Acute - pathology Liposomes Lymphokines - biosynthesis Lymphokines - genetics microparticles Monocytes - cytology Myeloid Cells - immunology Myeloid Cells - ultrastructure Neutrophils - immunology Neutrophils - ultrastructure Nickel - immunology Nickel - pharmacology Th2 Cells - cytology Toll-Like Receptor 4 - agonists Toll-Like Receptor 4 - immunology contact dermatitis microparticles inflammation regulation chemical sensitizer
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Summary:	A new mechanism of dendritic cell modulation by neutrophillike ectosomes in an in vitro model of nickel‐related allergic contact dermatitis. DCs are the first immune cells to be exposed to allergens, including chemical sensitizers, such as nickel, a human TLR4 agonist that induces DC maturation. In ACD, DCs can interact with PMNs that are recruited and activated, leading, in particular, to ectosome release. The objective of this work was to characterize the effects of PMN‐Ect on DC functions in an ACD context. We first developed a standardized protocol to produce, characterize, and quantify ectosomes by use of human PLB‐985 cells, differentiated into mature PMN (PLB‐Ect). We then studied the in vitro effects of these purified ectosomes on human moDC functions in response to NiSO4 and to LPS, another TLR4 agonist. Confocal fluorescence microscopy showed that PLB‐Ect was internalized by moDCs and localized in the lysosomal compartment. We then showed that PLB‐Ect down‐regulated NiSO4‐induced moDC maturation, as witnessed by decreased expression of CD40, CD80, CD83, CD86, PDL‐1, and HLA‐DR and by decreased levels of IL‐1β, IL‐6, TNF‐α, and IL‐12p40 mRNAs. These effects were related to p38MAPK and NF‐κB down‐regulation. However, no increase in pan‐regulatory DC marker genes (GILZ, CATC, C1QA) was observed; rather, levels of effector DC markers (Mx1, NMES1) were increased. Finally, when these PLB‐Ect + NiSO4‐treated moDCs were cocultured with CD4+ T cells, a Th2 cytokine profile seemed to be induced, as shown, in particular, by enhanced IL‐13 production. Together, these results suggest that the PMN‐Ect can modulate DC maturation in response to nickel, a common chemical sensitizer responsible for ADC.
Bibliography:	These authors contributed equally to the work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0741-5400 1938-3673
DOI:	10.1189/jlb.3A0314-132RR