Epithelial structure and homeostasis of the skin depend on the balance between cell survival and cell death. In inflammatory skin diseases (ISD) cell death mechanisms are often dysregulated. This study shows an important role of receptor-interacting protein kinase-3 (RIP3)-regulated necroptosis - one type of regulated necrosis - in keratinocytes besides apoptosis. We detected a significantly enhanced epidermal expression of RIP3 in lichen planus (LP) and lupus erythematosus (LE) in comparison to healthy and psoriasis skin biopsies. Additionally, the analysis of T cells from lesional LE and LP skin biopsies revealed a dominant type I immune response with high frequencies of IFN-γ and TNF-α positive cells. These findings indicated a role of IFN-γ and TNF-α in the induction of RIP3 and initiation of necroptosis. In vitro we showed that either IFN-γ or TNF-α but not IFN-α induced the production of RIP3 in keratinocytes and lead to cell swelling and vacuolization of keratinocytes in three-dimensional skin equivalents. Interestingly, shRNA knockdown of RIP3 prevented necroptosis of keratinocytes. Thus, necroptosis and RIP3 in particular represent potential targets for treatment of ISD like LE and LP.
Article info
Identification
Copyright
© 2018 Published by Elsevier Inc.
User license
Elsevier user license | How you can reuse 
Elsevier's open access license policy
Elsevier user license
Permitted
For non-commercial purposes:
- Read, print & download
- Text & data mine
- Translate the article
Not Permitted
- Reuse portions or extracts from the article in other works
- Redistribute or republish the final article
- Sell or re-use for commercial purposes
Elsevier's open access license policy
