IFN-κ Is a Rheostat for Development of Psoriasiform Inflammation

Psoriasis is a common, inflammatory autoimmune skin disease. Early detection of an IFN-1 signature occurs in many psoriasis lesions, but the source of IFN production remains debated. IFN-kappa is an important source of IFN-1 production in the epidermis. We identified a correlation between IFN-regulated and psoriasis-associated genes in human lesional skin. We thus wanted to explore the effects of IFN-kappa in psoriasis using the well-characterized imiquimod psoriasis model. Three mouse strains aged 10 weeks were used: wild-type C57Bl/6, C57Bl/6 that overexpress Ifnk in the epidermis (i.e., transgenic), and total body Ifnk(-/-) (i.e., knockout) strain. Psoriasis was induced by topical application of imiquimod on both ears for 8 consecutive days. Notably, the severity of skin lesions and inflammatory cell infiltration was more significantly increased in transgenic than in wild-type than in knockout mice. Gene expression analysis identified greater upregulation of Mxa, Il1b, Tnfa, Il6, Il12, Il23, Il17, and Ifng in transgenic compared to wild-type compared to knockout mice after imiquimod treatment. Furthermore, imiquimod increased CD8(+) and CD4(+) T-cell infiltration more in transgenic than in wild-type than in knockout mice. In summary, we identified IFN-k as a rheostat for initiation of psoriasiform inflammation. This suggests that targeting IFN-1s early in the disease may be an effective way of controlling psoriatic inflammation.

Automated summary

The study identified the important role of IFN-kappa in psoriasis lesions and its correlation with psoriasis-associated genes. Transgenic mice exhibited more severe skin lesions, inflammatory cell infiltration, and higher levels of inflammation-related gene expression compared to wild-type and knockout mice. This suggests that IFN-kappa acts as a rheostat for the initiation of psoriasiform inflammation, and targeting IFN-1s early in the disease may be an effective way of controlling psoriatic inflammation.