{"doi":"10.1101/2025.01.14.632971","title":"IL-21-STAT3 axis negatively regulates LAIR1 expression in B cells","abstract":"Abstract LAIR1 is an inhibitory receptor broadly expressed on human immune cells, including B cells. LAIR1 has been shown to modulate BCR signaling, however, it is still unclear whether its suppressive activity can be a negative regulator for autoreactivity. In this study, we demonstrate the LAIR1 expression profile on human B cells and prove its regulatory function and relationships to B cell autoreactivity. We show that both the frequency and level of LAIR1 expression decreases during B cell differentiation. LAIR1 expressing (LAIR1 + ) switched memory (SWM) B cells have a transcriptional profile less differentiated toward a plasma cell (PC) phenotype, harbor more autoreactive B cells and exhibit less PC differentiation in vitro than the LAIR1 negative (LAIR1 - ) counterpart. These data suggests that LAIR1 functions as a B cell tolerance checkpoint. We confirm previous data showing that patients with systemic lupus erythematosus (SLE) express less LAIR1 on B cells, implying a breakdown of the checkpoint, consistent with the enhanced PC differentiation seen in SLE. We further demonstrate that LAIR1 expression is down-regulated through the IL-21/STAT3 pathway which is known to be upregulated in SLE. These data suggest therapeutic targets that might decrease the aberrant PC differentiation observed in SLE.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":560556,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"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":877439,"name":"Izumi Kurata-Sato","orcid":"0000-0001-7815-9458","position":1,"is_corresponding":false},{"id":655282,"name":"Yemil Atisha‐Fregoso","orcid":"0000-0001-7702-8640","position":2,"is_corresponding":false},{"id":290028,"name":"Cynthia Aranow","orcid":"0000-0001-9299-0053","position":3,"is_corresponding":false},{"id":285336,"name":"Betty Diamond","orcid":"0000-0002-3250-3804","position":4,"is_corresponding":false},{"id":1462438,"name":"Kenji Yoshida","orcid":"0009-0003-4186-0437","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:55:42.883572Z","pmid":"39868127","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":[]}