Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/221115
Title: CARD14E138A signalling in keratinocytes induces TNF-dependent skin and systemic inflammation
Author: Manils Pacheco, Joan
Webb, Louise V.
Howes, Ashleigh
Janzen, Julia
Boeing, Stefan
Bowcock, Anne M.
Ley, Steven C.
Keywords: Psoriasi
Pèptids
Dermatitis
Animals
Psoriasis
Peptides
Dermatitis
Animals
Issue Date: 29-Jun-2020
Publisher: eLife Sciences
Abstract: To investigate how the CARD14E138A psoriasis-associated mutation induces skin inflammation, a knock-in mouse strain was generated that allows tamoxifen-induced expression of the homologous Card14E138A mutation from the endogenous mouse Card14 locus. Heterozygous expression of CARD14E138A rapidly induced skin acanthosis, immune cell infiltration and expression of psoriasis-associated pro-inflammatory genes. Homozygous expression of CARD14E138A 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. CARD14E138A-induced skin inflammation and systemic disease were independent of adaptive immune cells, ameliorated by blocking TNF and induced by CARD14E138A 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.
Note: Reproducció del document publicat a: https://doi.org/10.7554/eLife.56720
It is part of: eLife, 2020, vol. 9
URI: https://hdl.handle.net/2445/221115
Related resource: https://doi.org/10.7554/eLife.56720
ISSN: 2050-084X
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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