{"doi":"10.1172/jci.insight.149094","title":"Context-dependent induction of autoimmunity by TNF signaling deficiency","abstract":"TNF inhibitors are widely used to treat inflammatory diseases; however, 30%-50% of treated patients develop new autoantibodies, and 0.5%-1% develop secondary autoimmune diseases, including lupus. TNF is required for formation of germinal centers (GCs), the site where high-affinity autoantibodies are often made. We found that TNF deficiency in Sle1 mice induced TH17 T cells and enhanced the production of germline encoded, T-dependent IgG anti-cardiolipin antibodies but did not induce GC formation or precipitate clinical disease. We then asked whether a second hit could restore GC formation or induce pathogenic autoimmunity in TNF-deficient mice. By using a range of immune stimuli, we found that somatically mutated autoantibodies and clinical disease can arise in the setting of TNF deficiency via extrafollicular pathways or via atypical GC-like pathways. This breach of tolerance may be due to defects in regulatory signals that modulate the negative selection of pathogenic autoreactive B cells.","journal":"JCI Insight","year":2022,"id":281956,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":2391,"name":"Weiqing Huang","orcid":"0000-0001-7182-6123","position":1,"is_corresponding":false},{"id":919472,"name":"Ranjit Kumar Sahu","orcid":"0000-0003-2321-6798","position":2,"is_corresponding":false},{"id":957598,"name":"Catherine M.M. Diadhiou","orcid":"0000-0003-3389-5886","position":3,"is_corresponding":false},{"id":912223,"name":"Chirag Raparia","orcid":"0000-0002-5361-1257","position":4,"is_corresponding":false},{"id":958083,"name":"Roshawn Johnson","orcid":null,"position":5,"is_corresponding":false},{"id":958084,"name":"Tung Ming Leung","orcid":null,"position":6,"is_corresponding":false},{"id":832742,"name":"Susan Malkiel","orcid":null,"position":7,"is_corresponding":false},{"id":958085,"name":"Peta Gay Ricketts","orcid":null,"position":8,"is_corresponding":false},{"id":291653,"name":"Stefania Gallucci","orcid":"0000-0003-4737-8003","position":9,"is_corresponding":false},{"id":291657,"name":"Çağla Tükel","orcid":"0000-0001-7073-0226","position":10,"is_corresponding":false},{"id":338093,"name":"Chaim O. Jacob","orcid":null,"position":11,"is_corresponding":false},{"id":495675,"name":"Martin Lesser","orcid":"0000-0002-0318-5739","position":12,"is_corresponding":false},{"id":744453,"name":"Yong-Rui Zou","orcid":"0000-0002-3864-8908","position":13,"is_corresponding":false},{"id":285335,"name":"Anne Davidson","orcid":"0000-0002-4081-6464","position":14,"is_corresponding":false},{"id":928023,"name":"Tâm D. Quách","orcid":"0000-0003-2803-0909","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:29:15.734856Z","pmid":"35104241","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":[]}