{"doi":"10.1016/j.jid.2024.03.015","title":"The Switch/Sucrose Nonfermentable Subunit ARID1A Mediates Neutrophil-Associated Skin Inflammatory Responses","abstract":"AT-rich interaction domain 1A (ARID1A) is part of the Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex that plays important roles in development and disease by altering chromatin structure through ATP hydrolysis (Pulice and Kadoch, 2016Pulice J.L. Kadoch C. Composition and Function of Mammalian SWI/SNF Chromatin Remodeling Complexes in Human Disease.Cold Spring Harb Symp Quant Biol. 2016; 81: 53-60Crossref PubMed Scopus (74) Google Scholar). ARID1A binds to AT-rich DNA sequences through its ARID domain and is expressed in most cell types. ARID1A is one of the most heavily mutated SWI/SNF complex member and loss of function mutations has been linked to various cancers including endometrial, bladder, gastric, hepatocellular carcinoma, cholangiocarcinoma, melanoma, colorectal, lung, pancreatic, and breast cancer (Helming et al., 2014Helming K.C. Wang X. Roberts C.W.M. Vulnerabilities of mutant SWI/SNF complexes in cancer.Cancer Cell. 2014; 26: 309-317Abstract Full Text Full Text PDF PubMed Scopus (202) Google Scholar). In the skin, 45% of basosquamous cell carcinomas had ARID1A mutations (Chiang et al., 2019Chiang A. Tan C.Z. Kuonen F. Hodgkinson L.M. Chiang F. Cho R.J. et al.Genetic Mutations Underlying Phenotypic Plasticity in Basosquamous Carcinoma.J Invest Dermatol. 2019; 139: 2263-22671 e5Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar). Furthermore, dual deletion of Arid1a and Arid1b (paralog of Arid1a) in mice led to the rapid development of cutaneous squamous cell carcinoma(Wang et al., 2020Wang Z. Chen K. Jia Y. Chuang J.C. Sun X. Lin Y.H. et al.Dual ARID1A/ARID1B loss leads to rapid carcinogenesis and disruptive redistribution of BAF complexes.Nat Cancer. 2020; 1: 909-922Crossref Scopus (22) Google Scholar). In melanomas, loss of ARID1A resulted in diminished immune reactivity to the tumor due to decreased expression of interferon response genes (Li et al., 2020Li J. Wang W. Zhang Y. Cieslik M. Guo J. Tan M. et al.Epigenetic driver mutations in ARID1A shape cancer immune phenotype and immunotherapy.J Clin Invest. 2020; 130: 2712-2726Crossref PubMed Scopus (106) Google Scholar). Despite the importance of ARID1A in skin cancer, it is unclear whether it has any impacts on development, homeostasis, or inflammation of the skin. To study its role in the skin, we generated mice lacking Arid1a in epidermal stem cells by crossing Arid1afl/fl with keratin 14 (K14)-Cre mice. The homozygous mutants were born at the expected Mendelian ratios. However, the Arid1a knockout (KO) mice (Arid1afl/fl K14 Cre+) were significantly smaller as compared to the controls (CTL) by day 52 (Supplementary Figure 1a, 2b). CTL mice were a combination of Arid1a heterozygous and wildtype, keratin 14 Cre+ mice (Arid1awt/fl K14 Cre+ and Arid1awt/wt K14 Cre+). The smaller size of the knockout mice was not due to dehydration due to skin barrier impairment since new born KO mice were able to exclude the toluidine blue dye (Supplementary Figure 1b). Furthermore, the levels of transepidermal water loss was similar between control and KO mice at both days 6 and 7 suggesting that barrier impairment is not the cause for the smaller animal size (Supplementary Figure 1c-1d). Since the Keratin 14 promoter is also active in the esophagus, stomach, and oral palate we wanted to determine if there were any alterations in the structure of those tissue that could explain the smaller body size of the KO animals. In the esophagus and stomach there were no clear differences in the architecture of the epithelium at postnatal day 50 (Supplementary Figure 1e-1f). However in the oral palate, the Arid1a knockout mice had significant hyperplasia of the epithelium with ∼2 fold greater thickness than control mice (Supplementary Figure 1g-1h). The hyperplasia in the oral epithelium of the knockout mice was due to the two fold increase in proliferation (Supplementary Figure 1i-1j). This alteration in the oral palate could potentially lead to malnu","journal":"Journal of Investigative Dermatology","year":2024,"id":476547,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":432554,"name":"Yifang Chen","orcid":"0000-0002-0669-8994","position":1,"is_corresponding":false},{"id":486320,"name":"Ye Liu","orcid":"0000-0002-1901-669X","position":2,"is_corresponding":false},{"id":805666,"name":"Celia Fernández-Méndez","orcid":"0000-0001-8593-5507","position":3,"is_corresponding":false},{"id":1218129,"name":"Samiksha Mahapatra","orcid":"0000-0002-1226-9758","position":4,"is_corresponding":false},{"id":1314092,"name":"Sung Ha Lim","orcid":"0000-0002-2081-5261","position":5,"is_corresponding":false},{"id":1218130,"name":"Seung‐Phil Hong","orcid":"0000-0002-0684-498X","position":6,"is_corresponding":false},{"id":432555,"name":"George L. Sen","orcid":"0000-0003-1279-8550","position":7,"is_corresponding":false},{"id":1218128,"name":"Uyanga Batzorig","orcid":"0000-0001-8565-4713","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-19T02:06:29.605760Z","pmid":"38555061","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":[]}