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Mind Bomb 2 limits inflammatory dermatitis in Sharpin mutant mice independently of cell death

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. TNF and caspase-8-driven cell death causes the pathogenesis of Sharpincpdm mice, however, the role of MIB2, a pro-survival E3 ubiquitin ligase involved in TNF-signalling, in skin inflammation remains unknown. Here we demonstrate that MIB2 antagonises 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, G-CSF and Eotaxin, within the skin. This discovery advances our comprehension of inflammatory cytokines and chemokines involved in cpdm pathogenesis, and highlights the significance of MIB2 in inflammatory skin disease that is independent of its ability to regulate TNF-induced cell death.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skin, Fibroblast

SUBMITTER: Laura Dagley

LAB HEAD: Rebecca Feltham

PROVIDER: PXD045850 | Pride | 2024-01-25

REPOSITORIES: Pride

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			Action	DRS
	DIANN_libfree_230613.zip	Other
	Daniel_KO_10_1_1_11567.d.zip	Other
	Daniel_KO_11_1_1_11584.d.zip	Other
	Daniel_KO_12_1_1_11578.d.zip	Other
	Daniel_KO_13_1_1_11582.d.zip	Other

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