SkinChronicles, No 8, November 2025, by Florence Assan

Keratinocytes were known to participate in skin inflammatory responses by releasing proinflammatory cytokines such as IL-6, IL-8, and TNFα. In contrast, the production of type I interferons (IFNs) has traditionally been attributed to dendritic cells.

In this study, the authors demonstrate that epidermal keratinocytes represent a key source of IFN-β in psoriasis and wound repair. Using immunofluorescence, in vitro cell culture, and mouse models, they show that in keratinocytes, the antimicrobial peptide LL37 and double-stranded RNA (dsRNA) stimulate IFN-β production via the MAVS (mitochondrial antiviral-signaling protein) /TBK1(TANK-binding kinase 1)/AKT/IRF3(Interferon Regulatory Factor 3) signaling pathway. This activation induces the expression of IFN-stimulated genes and promotes the release of additional inflammatory cytokines, including IL-6, IL-8, and TNFα. Furthermore, the authors demonstrate that IFN-β drives the activation and maturation of dendritic cells.

This study highlights how environmental stressors stimulate epidermal keratinocytes to release IFN-β, thereby initiating a type I IFN response and activating downstream inflammatory pathways. These findings position keratinocytes as a key interface between environmental stimuli and the inflammatory cascade in wound repair and psoriasis.

Although psoriasis is traditionally considered a T-cell–mediated inflammatory disease, these results suggest that keratinocytes, the most abundant cells in the skin, play a key role by releasing IFN-β in response to injury, thereby activating dendritic cells.

Given my research interest in monogenetic models of psoriasis, this article provided me with new insights by positioning keratinocytes as central players in immune-mediated skin disorders, coordinating interactions with the environment, immune cells, and other skin cell types, including fibroblasts and melanocytes.

Paper: Ling-Juan Zhang, George L Sen, Nicole L Ward et al., Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injury, Immunity, 2016 Jul 19;45(1):119-30. doi: 10.1016/j.immuni.2016.06.021. DOI: 10.1016/j.immuni.2016.06.021