TWEAK functions with TNF and IL-17 on keratinocytes and is a potential target for psoriasis therapy.

ABSTRACT: TNF and IL-17 are two cytokines that drive dysregulated keratinocyte activity, and their targeting is highly efficacious in patients with psoriasis, but whether these molecules act with other inflammatory factors is not clear. Here, we show that mice having a keratinocyte-specific deletion of Fn14 (Tnfrsf12a), the receptor for the TNF superfamily cytokine TWEAK (Tnfsf12), displayed reduced imiquimod-induced skin inflammation, including diminished epidermal hyperplasia and less expression of psoriasis signature genes. This corresponded with Fn14 being expressed in keratinocytes in human psoriasis lesions and TWEAK being found in several subsets of skin cells. Transcriptomic studies in human keratinocytes revealed that TWEAK strongly overlaps with IL-17A and TNF in up-regulatin

SUBMITTER: Gupta RK 

PROVIDER: S-EPMC8756771 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature