IL-29 Exhibits Antiviral Activity by Inducing RIG-I and IFI-16 Expression in Oral Epithelial Cells

Abstract

Interleukin-29 (IL-29) is a cytokine belonging to the type Ⅲ interferon family, which regulates a similar set of genes as type Ⅰ interferons. Although type Ⅰ interferons act globally, type Ⅲ interferons primarily target epithelial cells and protect them against the frequent viral attacks that are common for barrier tissues. The antiviral effects of IL-29 have been demonstrated on barrier surfaces in the respiratory and gastrointestinal tracts, liver, blood-brain barrier, and skin, but it remains unknown whether IL-29 exhibits these effects in oral epithelial cells. In this study, we found that the functional IL-29 receptor, interferon-lambda receptor 1, is expressed in epithelial cells from both human oral mucosa and gingiva, but not inhuman gingival fibroblasts. Although IL-29 stimulation did not induce pro-inflammatory cytokine mRNA expressions, such as IL-6 and IL-8, it did induce retinoic acid inducible gene-I (RIG-I) and interferon-gamma-inducible protein 16 (IFI-16) production via a signal transducer and activator of transcription 1 (STAT1)-dependent pathway in gingival epithelial cells. RIG-I and IFI-16 sense viral nucleic acids, and the stimulation of these receptors induces interferon-beta production. Moreover, we confirmed that the augmenting effects of IL-29 on 5’ triphosphate double-stranded RNA (a synthetic ligand for RIG-I)-induced interferon-beta production in gingival epithelial cells. These data suggest the therapeutic potential of IL-29 for preventing viral infections in the oral mucosa.