1611 IFN-gamma causes keratinocyte necroptosis in acute graft-versus-host disease

Epidermal keratinocytes form the first cellular barrier of skin for protection against external injuries and maintenance local tissue homeostasis. Accordingly, epidermal destruction presents a central pathomechanism in type I inflammatory diseases such as acute graft-versus-host disease (aGVHD). In present work, we studied cell death context interferon-γ (IFNγ)-dependent aGVHD on culture level, translational organ cultures humanized mice. Expression nucleic acid sensor Z-DNA-binding protein 1 (ZBP1) was shown to cause necroptotic keratinocyte inflammation We sought characterize relevance ZBP1 necroptosis human 1-driven cutaneous aGVHD. here identify expression, interface dermatitis being hallmark expression dependent leukocyte-derived IFNγ interference with signaling by JAK inhibition prevented predominantly IL-17-driven psoriasis, both could not be detected. Of note, contrast mice affected receptor-interacting kinase (RIPK1) presence. These findings show that drives dominant immune responses may further point general role ZBP1-mediated necroptosis.