IL-25 in atopic dermatitis: a possible link between inflammation and skin barrier dysfunction?

Abstract

Atopic dermatitis (AD) is a common skin disease associated with a T(H)2 response and increased levels of T(H)2-associated cytokines and IgE. The mechanisms resulting in skewing the immune response in a T(H)2 direction in AD are not fully elucidated. However, such skewing has recently been associated with IL-25 in a murine model for allergic airway disease. The aim of this study was to investigate whether IL-25 may have a role in AD. We have identified IL-25-producing cells within the dermis of AD patients and propose that these cells are dendritic cells (DCs). This is supported by in vitro experiments that indicate that monocyte-derived DCs are capable of producing IL-25. As null mutations of filaggrin are associated with the development of an impaired skin barrier in AD, we investigated whether IL-25 affects filaggrin synthesis by keratinocytes. Using mRNA analysis, we have shown that IL-25 stimulation does indeed decrease filaggrin synthesis in cultured keratinocytes. These results suggest that IL-25 produced by DCs could have a dual role as both an inducer of the T(H)2 response and as an inhibitor of filaggrin synthesis, thereby directly affecting skin barrier function in AD patients.

• Authors: Malene Hvid, Christian Vestergaard, Kaare Kemp, Gitte B Christensen, Bent Deleuran, Mette Deleuran
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 131 Issue 1 Pg. 150-7 (Jan 2011) ISSN: 1523-1747 [Electronic] United States
• PMID: 20861853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FLG protein, human
• Filaggrin Proteins
• HLA-DR Antigens
• IL25 protein, human
• Interleukin-17
• Intermediate Filament Proteins
• RNA, Messenger
• Receptors, Interleukin-17

Topics

• Adult
• Cells, Cultured
• Dendritic Cells (cytology, immunology, metabolism)
• Dermatitis, Atopic (immunology, metabolism)
• Filaggrin Proteins
• Flow Cytometry
• HLA-DR Antigens (immunology, metabolism)
• Humans
• Interleukin-17 (genetics, immunology, metabolism)
• Intermediate Filament Proteins (immunology, metabolism)
• Keratinocytes (cytology, immunology, metabolism)
• Permeability
• RNA, Messenger (metabolism)
• Receptors, Interleukin-17 (immunology, metabolism)
• Th2 Cells (immunology, metabolism)