IL-25 Enhances HSV-1 Replication by Inhibiting Filaggrin Expression, and Acts Synergistically with Th2 Cytokines to Enhance HSV-1 Replication

• Published in: Journal of investigative dermatology Vol. 133; no. 12; pp. 2678 - 2685
• Main Authors: Kim, Byung Eui, Bin, Lianghua, Ye, Young-Min, Ramamoorthy, Preveen, Leung, Donald Y.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2013; Elsevier Limited
• Subjects: Atopic dermatitis; Biopsy; Dermatitis, Atopic - complications; Dermatitis, Atopic - metabolism; Dermatitis, Atopic - virology; Filaggrin Proteins; Gene Expression Regulation; Gene Silencing; Genotype; Herpes simplex virus 1; Herpesvirus 1, Human - physiology; Humans; Interferon-gamma - metabolism; Interleukin-13 - metabolism; Interleukin-17 - physiology; Interleukin-4 - metabolism; Intermediate Filament Proteins - metabolism; Kaposi Varicelliform Eruption - complications; Kaposi Varicelliform Eruption - metabolism; Kaposi Varicelliform Eruption - virology; Psoriasis - metabolism; RNA, Small Interfering - metabolism; Skin - metabolism; Skin Diseases - virology; Th2 Cells - metabolism; Vaccinia virus - metabolism; Virus Diseases - metabolism; Virus Replication
• ISSN: 0022-202X; 1523-1747; 1523-1747
• DOI: 10.1038/jid.2013.223

Atopic dermatitis (AD) is characterized by epidermal barrier defects and recurrent microbial skin infections. AD patients with a history of eczema herpeticum (ADEH+) have more severe skin disease and more highly T helper type 2 (Th2)–polarized immune responses as compared with uncomplicated AD (ADEH-). However, the mechanisms linking epidermal barrier defects and viral skin infection are not well understood. Recently, it has been reported that interleukin-25 may play a role in augmenting Th2 responses. We examined protein expression of IL-25 in the skin biopsies from normal subjects (n=10), ADEH- (n=18), ADEH+ (n=7), and psoriasis (n=9). IL-25 expression was increased in the skin from ADEH-, ADEH+, and psoriasis as compared with normal skin, and was significantly greater in lesional ADEH+ skin than in lesional ADEH- skin. Importantly, we demonstrated that IL-25 enhances herpes simplex virus (HSV)-1 and vaccinia virus replication by inhibiting filaggrin expression, and IL-25 acts synergistically with IL-4 and IL-13 to enhance HSV-1 replication in vitro. In contrast, IFN-γ inhibited HSV-1 replication in vitro. In addition, we demonstrate that filaggrin is a critical protein to inhibit HSV-1 replication because filaggrin small interfering RNA knockdown enhances HSV-1 replication in vitro. Filaggrin breakdown products, however, inhibited HSV-1 replication in vitro.