{"doi":"10.7554/elife.56720","title":"CARD14E138A signalling in keratinocytes induces TNF-dependent skin and systemic inflammation","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.","journal":"eLife","year":2020,"id":97186,"datarank":1.7568231882832968,"base_score":3.5263605246161616,"endowment":3.5263605246161616,"self_citation_contribution":0.5289540786924243,"citation_network_contribution":1.2278691095908725,"self_endowment_contribution":0.5289540786924243,"citer_contribution":1.2278691095908725,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"citer_count":29,"citers_with_citation_signal":24,"citers_with_endowment":24,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE149880","GSE75931","GSE73305","GSE52954"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":480968,"name":"Louise V. Webb","orcid":"0000-0001-6806-5589","position":1,"is_corresponding":false},{"id":480969,"name":"Ashleigh Howes","orcid":"0000-0001-9707-2067","position":2,"is_corresponding":false},{"id":481963,"name":"Julia Janzen","orcid":null,"position":3,"is_corresponding":false},{"id":480970,"name":"Stefan Boeing","orcid":"0000-0003-0495-5659","position":4,"is_corresponding":false},{"id":361598,"name":"A. Bowcock","orcid":"0000-0001-8691-9090","position":5,"is_corresponding":false},{"id":480971,"name":"Steven C. Ley","orcid":"0000-0001-5911-9223","position":6,"is_corresponding":false},{"id":480967,"name":"Joan Manils","orcid":"0000-0001-8429-1295","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T22:35:34.520494Z","pmid":"32597759","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}