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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