Document Detail


Generation and functional analysis of human TNF-α/iNOS-producing dendritic cells (Tip-DC).
MedLine Citation:
PMID:  23742057     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: A unique type of CD11c(pos) dendritic cells (DC) is abundant in inflamed tissue, for example, in chronic inflammatory skin diseases. Due to their remarkable production of tumor necrosis factor (TNF)-α and inducible NO synthase (iNOS), these cells have been referred to as TNF and iNOS-producing DC (Tip-DC). While Tip-DC have been mainly characterized in murine models of infection, functional data about their human counterpart are lacking. OBJECTIVES: We sought to generate human Tip-DC in vitro und thus provide a new model for the investigation of their phenotype and function. METHODS: We generated human Tip-DC from monocytic precursor cells of healthy individuals, atopic and psoriatic patients using human serum. Resting and stimulated cells were analyzed by flow cytometry, real-time PCR, and by ELISA. INOS activity was measured by fluorometric detection of NO. RESULTS: Tip-DC closely resembled their in vivo counterparts by expressing CD11c, CD86, and CD40 while lacking CD1a, CD1c, or CD207/Langerin. Bacterial stimulation of Tip-DC from healthy donors, atopic dermatitis, or psoriasis patients resulted in a similar increase in iNOS activity and TNF-α production. In kinetic experiments, TNF-α, a putative activator of Tip-DC, could not induce NOS2. Upon bacterial stimulation, TNFA, IL6, IL12B, and IL23A mRNA appeared in a first wave, while IL12A and NOS2 mRNA were up-regulated later on but not blocked by anti-TNF-α agents, implying a biphasic pro-inflammatory response. CONCLUSIONS: We developed a new model for the study of human Tip-DC and provide the first evidence of their pro-inflammatory capacity.
Authors:
D Wilsmann-Theis; S Koch; C Mindnich; S Bonness; S Schnautz; D von Bubnoff; T Bieber
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-6-6
Journal Detail:
Title:  Allergy     Volume:  -     ISSN:  1398-9995     ISO Abbreviation:  Allergy     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-6-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804028     Medline TA:  Allergy     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Affiliation:
Department of Dermatology and Allergy, Rheinische Friedrich Wilhelms University of Bonn, Bonn, Germany.
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