부산대학교 도서관

To investigate how the CARD14.sup.E138A psoriasis-associated mutation induces skin inflammation, a knock-in mouse strain was generated that allows tamoxifen-induced expression of the homologous Card14.sup.E138A mutation from the endogenous mouse Card14 locus. Heterozygous expression of CARD14.sup.E138A rapidly induced skin acanthosis, immune cell infiltration and expression of psoriasis-associated pro-inflammatory genes. Homozygous expression of CARD14.sup.E138A induced more extensive skin inflammation and a severe systemic disease involving infiltration of myeloid cells in multiple organs, temperature reduction, weight loss and organ failure. This severe phenotype resembled acute exacerbations of generalised pustular psoriasis (GPP), a rare form of psoriasis that can be caused by CARD14 mutations in patients. CARD14.sup.E138A-induced skin inflammation and systemic disease were independent of adaptive immune cells, ameliorated by blocking TNF and induced by CARD14.sup.E138A signalling only in keratinocytes. These results suggest that anti-inflammatory therapies specifically targeting keratinocytes, rather than systemic biologicals, might be effective for GPP treatment early in disease progression.
Byline: Joan Manils, Louise V Webb, Ashleigh Howes, Julia Janzen, Stefan Boeing, Anne M Bowcock, Steven C Ley Introduction Psoriasis is a chronic auto-immune skin disease that affects 2--3% of [...]