{"doi":"10.1101/2021.03.12.435182","title":"Context-dependent miR-21 regulation of TLR7-mediated autoimmune and foreign antigen driven antibody-forming cell and germinal center responses","abstract":"Abstract MicroRNAs (miRNAs) are involved in healthy B cell responses and the loss of tolerance in systemic lupus erythematosus (SLE), though the role of many miRNAs remains poorly understood. Dampening miR-21 activity was previously shown to reduce splenomegaly and blood urea nitrogen levels in SLE-prone mice, but the detailed cellular responses and mechanism of action remains unexplored. Herein, using the TLR7 agonist imiquimod-induced SLE model, we observed that loss of miR-21 in Sle1b mice prevented the formation of plasma cells and autoantibody forming cells (AFC), without a significant effect on the magnitude of the germinal center (GC) response. We further observed reduced dendritic cell and monocyte numbers in the spleens of miR-21 deficient Sle1b ( Sle1b .miR-21KO) mice that were associated with reduced interferon, proinflammatory cytokines, and effector CD4 + T cell responses. RNAseq analysis on B cells from Sle1b .miR-21KO mice revealed reduced activation and response to interferon and cytokine and target array analysis revealed modulation of numerous miR-21 target genes in response to TLR7 activation and type I interferon stimulation. Our findings in the B6. Sle1b .Yaa spontaneous model recapitulated the miR-21 role in TLR7-induced responses with an additional role in autoimmune GC and Tfh responses. Finally, immunization with T-dependent antigen revealed a role for miR-21 in foreign antigen driven GC and Ab, but not AFC responses. Our data suggest a potential multifaceted, context-dependent role for miR-21 in autoimmune and foreign antigen driven AFC and GC responses. Further study is warranted to delineate the cell-intrinsic requirements and mechanisms of miR-21 during infection and SLE development. Key Points miR-21 has context dependent effects on AFC and GC responses miR-21 promotes TLR7-driven autoimmunity with activation of multiple B cell pathways miR-21 is required for optimal B cell responses to T-dependent foreign antigen","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":218506,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"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":0.9466,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":788943,"name":"Kristen N Bricker","orcid":"0000-0001-8963-9780","position":1,"is_corresponding":false},{"id":262129,"name":"Adam J. Fike","orcid":"0000-0002-7105-6162","position":2,"is_corresponding":false},{"id":413546,"name":"Sathi Babu Chodisetti","orcid":"0000-0001-7473-9420","position":3,"is_corresponding":false},{"id":413547,"name":"Phillip P. Domeier","orcid":"0000-0002-9937-8251","position":4,"is_corresponding":false},{"id":413548,"name":"Nicholas Choi","orcid":"0000-0003-4801-4973","position":5,"is_corresponding":false},{"id":816653,"name":"Melinda J Fasnacht","orcid":null,"position":6,"is_corresponding":false},{"id":816265,"name":"Sara Luckenbill","orcid":"0000-0002-8035-2246","position":7,"is_corresponding":false},{"id":239697,"name":"Steven F. Ziegler","orcid":"0000-0003-0657-5529","position":8,"is_corresponding":false},{"id":413549,"name":"Ziaur S. M. Rahman","orcid":"0000-0001-8431-9681","position":9,"is_corresponding":false},{"id":686517,"name":"Stephanie L Schell","orcid":"0000-0001-5963-4938","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:29.626149Z","pmid":null,"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":[]}