Mind bomb 2 limits inflammatory dermatitis in Sharpin mutant mice independently of cell death
- Author(s)
- Simpson, DS; Anderton, H; Yousef, J; Vaibhav, V; Cobbold, SA; Bandala-Sanchez, E; Kueh, AJ; Dagley, LF; Herold, MJ; Silke, J; Vince, JE; Feltham, R;
- Details
- Publication Year 2024-01,Volume 3,Issue #1,Page pgad438
- Journal Title
- PNAS Nexus
- Abstract
- Skin inflammation is a complex process implicated in various dermatological disorders. The chronic proliferative dermatitis (cpd) phenotype driven by the cpd mutation (cpdm) in the Sharpin gene is characterized by dermal inflammation and epidermal abnormalities. Tumour necrosis factor (TNF) and caspase-8-driven cell death causes the pathogenesis of Sharpin(cpdm) mice; however, the role of mind bomb 2 (MIB2), a pro-survival E3 ubiquitin ligase involved in TNF signaling, in skin inflammation remains unknown. Here, we demonstrate that MIB2 antagonizes inflammatory dermatitis in the context of the cpd mutation. Surprisingly, the role of MIB2 in limiting skin inflammation is independent of its known pro-survival function and E3 ligase activity. Instead, MIB2 enhances the production of wound-healing molecules, granulocyte colony-stimulating factor, and Eotaxin, within the skin. This discovery advances our comprehension of inflammatory cytokines and chemokines associated with cpdm pathogenesis and highlights the significance of MIB2 in inflammatory skin disease that is independent of its ability to regulate TNF-induced cell death.
- Keywords
- Sharpin; Tnf; cpdm; dermatitis; mind bomb 2
- Research Division(s)
- Inflammation; Advanced Technology And Biology; Blood Cells And Blood Cancer; Immunology; Ubiquitin Signalling
- PubMed ID
- 38156288
- Publisher's Version
- https://doi.org/10.1093/pnasnexus/pgad438
- Open Access at Publisher's Site
https://doi.org/10.1093/pnasnexus/pgad438- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
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Creation Date: 2024-01-25 09:18:10
Last Modified: 2024-01-25 10:58:44