The proteolytic activity of the major dust mite allergen Der p 1 conditions dendritic cells to produce less interleukin-12: allergen-induced Th2 bias determined at the dendritic cell level.
BACKGROUND
The proteolytic activity of the house dust mite allergen Der p 1 has recently been shown to bias Th cell subset development in favour of Th2. Apart from its direct effect on T cells, it is conceivable that the proteolytic activity of Der p 1 may induce the generation of dendritic cells (DCs) that favour a Th2 response.


OBJECTIVE
To study the effect of the proteolytic activity of Der p 1 on DC functions; namely cell surface phenotype, IL-12 production and ability to favour a Th2 response.


METHODS
We have generated immature DCs from peripheral blood monocytes, matured them with LPS in the presence of either proteolytically active or inactive Der p 1 and compared their functions using flow cytometric analysis.


RESULTS
Here we demonstrate for the first time that DCs that have been matured in the presence of proteolytically active Der p 1 produce significantly less IL-12, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1. The suppression of IL-12 production was due to the cleavage of CD40 by the proteolytic activity of Der p 1, hence rendering the DCs less responsive to stimulation through the CD40L-CD40 pathway. Furthermore, we demonstrate that DCs that have been matured in the presence of proteolytically active Der p 1 induce the production of significantly less IFN-gamma and more IL-4 by CD4 T cells, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1.


CONCLUSIONS
Collectively, our data provide compelling evidence for the role of the proteolytic activity of Der p 1 in directing DCs to induce Th2 subset development.
Ghaemmaghami
A M
AM
Division of Molecular & Clinical Immunology, Faculty of Medicine and Health Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
Gough
L
L
Sewell
H F
HF
Shakib
F
F
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000494:pharmacology*; D060829:Arthropod Proteins; D015415:Biomarkers / Q000032:analysis; D019013:CD40 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology*
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D015415:Biomarkers; D019013:CD40 Antigens; D008070:Lipopolysaccharides; D018664:Interleukin-12; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1