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

Ghaemmaghami, A. M.; Gough, L.; Sewell, H. F.; Shakib, F.

Abstract

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 lL-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.

Citation

Ghaemmaghami, A. M., Gough, L., Sewell, H. F., & Shakib, F. (2002). 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. Clinical and Experimental Allergy, 32(10), 1468-1475. https://doi.org/10.1046/j.1365-2745.2002.01504.x

• Journal Article Type: Article
• Acceptance Date: Oct 2, 2002
• Online Publication Date: Oct 8, 2002
• Publication Date: 2002-10
• Deposit Date: Jan 3, 2023
• Journal: Clinical and Experimental Allergy
• Print ISSN: 0954-7894
• Electronic ISSN: 1365-2222
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 32
• Issue: 10
• Pages: 1468-1475
• DOI: https://doi.org/10.1046/j.1365-2745.2002.01504.x
• Public URL: https://nottingham-repository.worktribe.com/output/3097652
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2745.2002.01504.x