Background/Purpose: Psoriasis is a one of the most common chronic inflammatory autoimmune skin diseases characterized by hyperproliferation and abnormal differentiation of keratinocytes and infiltration of inflammatory cells. It affects about 3% of the world’s population, with unknown etiology. In psoriasis, a complex network of cytokines and chemokines is produced by various types of immune cells, but keratinocytes also play a key role in pathogenesis. Early infiltration of plasmacytoid dendritic cells and detection of an interferon (IFN) signature occurs in many psoriasis lesions.  In addition, deletion of the type I IFN receptor is protective in imiquimod-induced psoriasis.  Recently, we described keratinocyte production of IFN-κ as an important source of type I IFN production in the epidermis.  We thus wanted to explore the role of IFN-κ in psoriasis. 

Methods: We used the well-characterized imiquimod (IMQ) psoriasis model for these studies. 10-week old male and female wild type (WT) and mice transgenic for IFN-κ under the K14 promoter (resulting in only epidermal overexpression) were used (n=5-8 per group).  Psoriasis was induced by topical application of IMQ on both ears for 8 consecutive days.  Control mice received Vaseline. Animals were monitored daily for ear thickness, lesion severity, and body weight. On day nine, mice were euthanized and disease severity was compared between WT and IFN-κ transgenic mice. Skin inflammation was assessed via H&E staining.

Results: Although both IFN-κ transgenic and WT IMQ treated mice exhibited psoriasis lesions in both ears after 8 days of treatment, the lesion size and thickness was significantly increased in IFN-κ transgenic mice vs. WT for both male and female mice. Interestingly, the difference was more exaggerated in IFN-κ transgenic female mice vs. male mice.  H&E staining revealed increased inflammatory cell infiltrates in IMQ treated IFN-κ-TG vs. WT mice. Control mice did not show any sign of inflammation or disease. Ongoing studies are characterizing the differences in cell populations that make up the inflammatory infiltrates in WT vs. IFN-κ transgenic mice.

Conclusion: Overexpression of IFN- κ in the epidermis caused accelerated and increased disease severity after topical application of IMQ. This suggests that overproduction of type I IFNs may impact psoriasis development and there may be a role of targeting IFNs in early disease. Further studies will need to elucidate the specific mechanisms that may be at play.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-kappa-promotes-the-development-of-psoriasis/