The skin disease erythrokeratoderma variabilis (EKV) has been shown to be associated with mutations in GJB3 and GJB4 encoding connexin (Cx)31 and Cx30.3, respectively.
FACS analysis of WT and mutant EGFP-Cx31 transfected keratinocytes revealed a high percentage of cell death associated with the skin disease-associated mutant Cx31 proteins.
Recently, we identified several missense mutations of the connexin gene GJB3 encoding connexin 31 (Cx31) in erythrokeratodermia variabilis (EKV), an autosomal dominant skin disorder.
One theory for the pathophysiology of photosensitive autoimmune skin diseases is that photoinduction of tumor necrosis factor alpha (TNFalpha) secretion leads to keratinocyte apoptosis and translocation of previously sequestered cellular antigens that then activate the immune system.
Recently, mutations in two gap junction genes, GJB2 and GJB3 (encoding Connexin 26 and Connexin 31, respectively), have been shown to underlie either inherited hearing loss and skin disease or both disorders.
Elafin is induced in epidermis in skin disorders with dermal neutrophilic infiltration: interleukin-1 beta and tumour necrosis factor-alpha stimulate its secretion in vitro.
Recently, mutations in two gap junction genes, GJB2 and GJB3 (encoding Connexin 26 and Connexin 31, respectively), have been shown to underlie either inherited hearing loss and skin disease or both disorders.
We report a missense mutation in the gap junction protein beta-3 (encoding Connexin 31), which was detected in only the affected members of a family in which the autosomal dominant skin disease erythrokeratoderma variabilis was segregating.
IL-1β has emerged as pivotal for promoting inflammation, particularly in autoinflammatory diseases, whereas IL-1α and the IL-36 subfamily are associated with skin diseases.
Null and missense mutations in the genes encoding interleukin (IL)-1 family (IL-1 and IL-36) anti-inflammatory receptor antagonist (Ra) cytokines can underlie the development of severe pustular dermatoses.
In summary, dysregulated expression of novel agonistic and antagonistic IL-1 family member ligands can promote cutaneous inflammation, revealing potential novel targets for the treatment of inflammatory skin disorders.