Interferons (IFNs) are “warning signal” cytokines released upon pathogen sensing. IFNs control the expression of interferon-stimulated genes (ISGs), which are often crucial to restrict viral infections and establish a cellular antiviral state.1,2 Langerin (CD207), a well-known surface receptor on Langerhans cells (LC), belongs to the C-type lectin receptor (CLR) family and constitutes a major pathogen binding receptor able to regulate both innate and adaptive immune responses.3,4 Importantly, this CLR was reported as an antiviral receptor, notably able to bind and internalize incoming human immunodeficiency virus (HIV) virions in Birbeck granules for degradation.5,6 However, langerin was never viewed as a contributor to the interferon-mediated antiviral immune response. We now provide evidence that langerin is an ISG showing upregulated expression upon IFN treatment in monocyte-derived and ex vivo human skin-isolated LCs.