Session Type: Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Psoriasis is a common, chronic inflammatory autoimmune skin diseases characterized by hyperproliferation and abnormal differentiation of keratinocytes and infiltration of inflammatory cells. Early infiltration of plasmacytoid dendritic cells and detection of an interferon (IFN) signature occurs in many psoriasis lesions. Recently, we described keratinocyte production of interferon kappa (IFNk) as an important source of type I IFN production in the epidermis. We thus wanted to explore the role of IFNk 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 Ifnk (TG) expressed under the K14 promoter (thus inducing expression only in the epidermis) and mice deficient for Ifnk ( KO) were used. Psoriasis was induced by topical application of IMQ on both ears for 8 consecutive days (n=6-10 mice per each group. Control mice received Vaseline (n=10 mice per each group). Animals were monitored daily for ear thickness, lesion severity, and body weight and photo were taken daily. On day nine, mice were euthanized, and disease severity were compared among all groups via RT-qPCR, immunohistochemistry, and flow cytometry.
Results: For all evaluations, untreated mice did not show any sign of inflammation or disease. While all IMQ treated mice exhibited psoriasis lesions in both ears after 8 days of treatment, development of splenomegaly, ear thickness, cutaneous lesion size and spleen weight were significantly higher in TG mice (p< .001) vs. WT for both male and female mice. The spleen size and ear thickness were significantly smaller in KO mice compared to WT (p< .01). Interestingly, the difference was more exaggerated in TG female vs. male mice. H&E staining revealed higher number of inflammatory cell infiltrates in IMQ treated TG vs. WT and fewer inflammatory infiltrates in KO mice. IL-17 and CD8 co-staining of ear tissues revealed greater number of CD8 and IL-17 double-positive cells in IMQ treated TG > WT >KO mice in both male and female groups. Gene expression for type I IFNs, the IFN-regulated gene Mx1, Stat3, and inflammatory cytokines, Il1b, Il17, Tnfa, Il6, Il12 and Il23 were significantly higher in IMQ treated TG >WT >KO (p< 0.05 for all genes tested). While both TG and WT mice demonstrated influx of monocytes by flow cytometry, KO mice did not exhibit a detectible increase after IMQ treatment. No difference in plasmacytoid dendritic cell recruitment was noted between groups.
Conclusion: Overexpression of Ifnk in the epidermis results in increased disease severity after topical application of IMQ, whereas deletion of Ifnk attenuated disease. Although, overexpression of Ifnk alone in the skin does not trigger skin inflammation, our data suggests that epidermal type I IFNs may trigger may act as a rheostat for psoriasis inflammatory responses, driving more inflammatory cells in the skin and promoting a heightened inflammatory and IL-17-oriented response. Together, these data suggest 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, especially in human skin.
To cite this abstract in AMA style:Gharaee-Kermani M, Estadt S, Wolf-Fortune S, Liu J, Reed T, Gudjonsson J, Kahlenberg J. The Role of Interferon Kappa in Psoriasis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/the-role-of-interferon-kappa-in-psoriasis/. Accessed November 23, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-role-of-interferon-kappa-in-psoriasis/