期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 142, 期 1, 页码 155-+出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2021.05.029
关键词
-
类别
资金
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (Bethesda, MD) of the National Institutes of Health [R01-AR071384, R01-AR060802, P30-AR075043, P50-AR070590]
- A. Alfred Taubman Medical Research Institute (Ann Arbor, MI)
- Parfet Emerging Scholar Award
- National Psoriasis Foundation
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.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据