Interferon-Lambda: A Key Cytokine for Dendritic Cell Development?

Abstract

Abstract In light of the current pandemic, COVID-19, our understanding of how the immune system combats viral infection has become more important than ever. Interferons (IFNs) are an integral component of the immune system’s anti-viral response. While the functions of Type I Interferons have been extensively studied, the newest member of the Interferon family, Interferon-Lambda (IFN-λ), is yet to be fully investigated. Currently, it is believed that the canonical signalling pathway of the IFN-λ receptor (R, defined as IFN-λR1 and IL-10Rb) is shared with Type I IFN-αR signalling and leads to the transcription of Interferon Stimulated Genes (ISGs), key genes involved in antiviral immunity. However, there is a growing body of evidence that indicates that IFN-λR1 is involved in signalling pathways that differ to IFN-αR. Notably amongst this evidence is IFN-λR1’s restricted expression to epithelial and some haematopoietic cells as well as non-redundant roles being discovered at mucosal barriers. Building on novel preliminary data, this project seeks to differentiate IFN-λR1 signalling from this canonical pathway and determine whether other receptor chains are involved. Dendritic Cells (DCs), key mediators linking innate and adaptive immunity, are the focus of this project as they are major producers of IFN-λ and are also one of the few haematopoietic cells which express IFN-λR1. Using DCs, this project will investigate the signalling pathways regulated by IFN-λR1 and other potential pathways instigated by the interaction between IFN-λR1 and other receptors. Additionally, this work will focus on how IFN-λ signalling contributes to cellular function in the context of DC differentiation and development.