{"doi":"10.4049/jimmunol.2100186","title":"HERV1-env Induces Unfolded Protein Response Activation in Autoimmune Liver Disease: A Potential Mechanism for Regulatory T Cell Dysfunction","abstract":"Regulatory T cells (Tregs) are not terminally differentiated but can acquire effector properties. Here we report an increased expression of human endogenous retrovirus 1 (HERV1-env) proteins in Tregs of patients with de novo autoimmune hepatitis and autoimmune hepatitis, which induces endoplasmic reticulum (ER) stress. HERV1-env-triggered ER stress activates all three branches (IRE1, ATF6, and PERK) of the unfolded protein response (UPR). Our coimmunoprecipitation studies show an interaction between HERV1-env proteins and the ATF6 branch of the UPR. The activated form of ATF6α activates the expression of RORC and STAT3 by binding to promoter sequences and induces IL-17A production. Silencing of HERV1-env results in recovery of Treg suppressive function. These findings identify ER stress and UPR activation as key factors driving Treg plasticity (species: human).","journal":"The Journal of Immunology","year":2023,"id":370656,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"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":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":927836,"name":"Saikat Paul","orcid":"0000-0003-3670-4125","position":1,"is_corresponding":false},{"id":328129,"name":"Andrew E. Libby","orcid":"0000-0003-3726-2170","position":2,"is_corresponding":false},{"id":686665,"name":"Jordan Patterson","orcid":"0000-0002-9474-4187","position":3,"is_corresponding":false},{"id":1130010,"name":"Adam S. Arterbery","orcid":"0000-0002-3817-890X","position":4,"is_corresponding":false},{"id":333804,"name":"James Knight","orcid":"0000-0003-1166-0437","position":5,"is_corresponding":false},{"id":107011,"name":"Christopher Castaldi","orcid":"0000-0003-4880-801X","position":6,"is_corresponding":false},{"id":1130011,"name":"Guilin Wang","orcid":"0000-0001-5075-9048","position":7,"is_corresponding":false},{"id":1080632,"name":"Yaron Avitzur","orcid":"0000-0002-8072-5727","position":8,"is_corresponding":false},{"id":239748,"name":"Mercedes Martínez","orcid":"0000-0001-6128-0155","position":9,"is_corresponding":false},{"id":1130363,"name":"Steve Lobritto","orcid":null,"position":10,"is_corresponding":false},{"id":291201,"name":"Yanhong Deng","orcid":"0000-0001-6873-8026","position":11,"is_corresponding":false},{"id":1130364,"name":"Gan Geliang","orcid":null,"position":12,"is_corresponding":false},{"id":239668,"name":"Alexander Kroemer","orcid":"0000-0002-9842-4973","position":13,"is_corresponding":false},{"id":633941,"name":"Thomas Fishbein","orcid":"0009-0009-8181-1828","position":14,"is_corresponding":false},{"id":97277,"name":"Andrew L. Mason","orcid":"0000-0002-0470-9522","position":15,"is_corresponding":false},{"id":278062,"name":"Margarita Dominguez‐Villar","orcid":"0000-0002-9719-0028","position":16,"is_corresponding":false},{"id":315497,"name":"Malaiyalam Mariappan","orcid":"0000-0002-2966-1182","position":17,"is_corresponding":false},{"id":1130365,"name":"Udeme D Ekong","orcid":null,"position":18,"is_corresponding":false},{"id":1130009,"name":"Kumar Subramanian","orcid":"0000-0002-9009-3313","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:15:41.237096Z","pmid":"36722941","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":[]}