{"doi":"10.1084/jem.20240272","title":"Dominant interfering CARD11 variants disrupt JNK signaling to promote GATA3 expression in T cells","abstract":"Several \"primary atopic disorders\" are linked to monogenic defects that attenuate TCR signaling, favoring T helper type 2 (TH2) cell differentiation. Patients with CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease suffer from severe atopy, caused by germline loss-of-function/dominant interfering (LOF/DI) CARD11 variants. The CARD11 scaffold enables TCR-induced activation of NF-κB, mTORC1, and JNK signaling, yet the function of CARD11-dependent JNK signaling in T cells remains nebulous. Here we show that CARD11 is critical for TCR-induced activation of JNK1 and JNK2, as well as canonical JUN/FOS AP-1 family members. Patient-derived CARD11 DI variants attenuated WT CARD11 JNK signaling, mirroring effects on NF-κB. Transcriptome profiling revealed JNK inhibition upregulated TCR-induced expression of GATA3 and NFATC1, key transcription factors for TH2 cell development. Further, impaired CARD11-JNK signaling was linked to enhanced GATA3 expression in CADINS patient T cells. Our findings reveal a novel intrinsic mechanism connecting impaired CARD11-dependent JNK signaling to enhanced GATA3/NFAT2 induction and TH2 cell differentiation in CADINS patients.","journal":"The Journal of Experimental Medicine","year":2025,"id":530015,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9479,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1409360,"name":"Jeffrey R. Stinson","orcid":"0000-0002-4157-3185","position":1,"is_corresponding":false},{"id":997211,"name":"Melissa A. Kallarakal","orcid":"0009-0000-9948-3871","position":2,"is_corresponding":false},{"id":505196,"name":"Lei Huang","orcid":"0000-0002-1491-3869","position":3,"is_corresponding":false},{"id":553992,"name":"Andrew M. Frank","orcid":"0000-0003-0411-7102","position":4,"is_corresponding":false},{"id":295313,"name":"Gauthaman Sukumar","orcid":"0000-0003-3129-4171","position":5,"is_corresponding":false},{"id":280628,"name":"Nermina Saucier","orcid":"0009-0004-8992-1427","position":6,"is_corresponding":false},{"id":241309,"name":"Clifton L. Dalgard","orcid":"0000-0003-2025-8239","position":7,"is_corresponding":false},{"id":295449,"name":"Alice Chan","orcid":"0000-0003-1466-7044","position":8,"is_corresponding":false},{"id":225938,"name":"Joshua D. Milner","orcid":"0000-0002-3913-3869","position":9,"is_corresponding":false},{"id":241308,"name":"Megan A. Cooper","orcid":"0000-0002-5696-172X","position":10,"is_corresponding":false},{"id":241321,"name":"Andrew L. Snow","orcid":"0000-0002-8728-6691","position":11,"is_corresponding":false},{"id":720899,"name":"Bradly M. Bauman","orcid":"0000-0002-4471-0966","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:51:01.235017Z","pmid":"40111223","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":[]}