WTAP-mediated m6A modification of IFNE is required for antiviral defense in condyloma acuminata.

BACKGROUND: IFN-ε is essential in combating viral infections, particularly in epithelial cells and protected mucosal tissues. Its protective effects have been demonstrated against HSV2, Zika virus, HIV and SARS-COV2. However, the specific expression and role of IFN-ε in skin keratinocytes and HPV infection are still not fully understood and require further investigation. OBJECTIVE: In this study, we aimed to investigate the functions and expression mechanism of IFN-ε in keratinocytes during HPV infection and the progression of condyloma acuminata. METHODS: Keratinocytes isolated from biopsied CA warts and normal skins samples were analyzed by MeRIP-seq analysis. IFN-ε and WTAP in CA warts and normal skins were analyzed by immunostaining and qPCR. RESULTS: In this study, we identified IFN-ɛ was markedly upregulated in CA warts and HPV-infected keratinocytes. IFN-ɛ expression also showed negatively correlation with the size of CA warts (R=-0.4646, P = 0.009). IFN-ɛ suppressed the susceptibility of HPV infection directly. m6A analysis reveals WTAP is a key m6A writer promoting the m6A modification of IFNE mRNA. CONCLUSION: Our research suggests that IFN-ɛ is an important Type I IFN cytokine involved in the development of genital warts. Furthermore, we found that HPV infection affects the m6A modifications of IFNE through a mechanism dependent on WTAP. This study provides insights into the innate immune response of the host to HPV infection and may contribute to the development of future strategies for regulating innate immunity to treat genital warts.

Chemerin Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production.

OBJECTIVE: Psoriasis is often combined with metabolic abnormalities, such as obesity and diabetes. The upregulation of chemerin, which is an essential protein produced primarily from white fat, is strongly correlated to the development of psoriasis. However, there is no clarification on its exact function and mechanism in disease pathogenesis. The present study aims to determine its function and mechanism in disease pathogenesis. METHODS: The present study used a psoriasislike inflammatory cell model and imiquimod (IMQ)-induced mouse model to confirm whether chemerin is upregulated in psoriasis patients. RESULTS: Chemerin enhanced the keratinocyte proliferation, inflammatory cytokine secretion, and activation of the MAPK signaling pathway. Crucially, the intraperitoneal injection of neutralizing anti-chemerin antibody (ChAb) diminished the epidermal proliferation and inflammation in the IMQ-induced mouse model. CONCLUSION: The present results indicate that chemerin promotes keratinocyte proliferation, and enhances the production of inflammatory cytokines, thereby aggravating the psoriasis. Thus, chemerin can be a prospective target for the treatment of psoriasis.