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

Summary 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‐γ 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.