{"doi":"10.1172/jci.insight.159751","title":"Distinct pathogenic roles for resident and monocyte-derived macrophages in lupus nephritis","abstract":"Lupus nephritis is a serious complication of systemic lupus erythematosus, mediated by IgG immune complex (IC) deposition in kidneys, with limited treatment options. Kidney macrophages are critical tissue sentinels that express IgG-binding Fcγ receptors (FcγRs), with previous studies identifying prenatally seeded resident macrophages as major IC responders. Using single-cell transcriptomic and spatial analyses in murine and human lupus nephritis, we sought to understand macrophage heterogeneity and subset-specific contributions in disease. In lupus nephritis, the cell fate trajectories of tissue-resident (TrMac) and monocyte-derived (MoMac) kidney macrophages were perturbed, with disease-associated transcriptional states indicating distinct pathogenic roles for TrMac and MoMac subsets. Lupus nephritis-associated MoMac subsets showed marked induction of FcγR response genes, avidly internalized circulating ICs, and presented IC-opsonized antigen. In contrast, lupus nephritis-associated TrMac subsets demonstrated limited IC uptake, but expressed monocyte chemoattractants, and their depletion attenuated monocyte recruitment to the kidney. TrMacs also produced B cell tissue niche factors, suggesting a role in supporting autoantibody-producing lymphoid aggregates. Extensive similarities were observed with human kidney macrophages, revealing cross-species transcriptional disruption in lupus nephritis. Overall, our study suggests a division of labor in the kidney macrophage response in lupus nephritis, with treatment implications - TrMacs orchestrate leukocyte recruitment while MoMacs take up and present IC antigen.","journal":"JCI Insight","year":2022,"id":236770,"datarank":0.6329261557764161,"base_score":4.219507705176107,"endowment":4.219507705176107,"self_citation_contribution":0.6329261557764161,"citation_network_contribution":0.0,"self_endowment_contribution":0.6329261557764161,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":67,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"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":235856,"name":"Zewen Kelvin Tuong","orcid":"0000-0002-6735-6808","position":1,"is_corresponding":false},{"id":242954,"name":"Kevin W. Loudon","orcid":"0000-0001-9055-6894","position":2,"is_corresponding":false},{"id":658495,"name":"Eduardo Patiño‐Martínez","orcid":"0000-0002-5986-1257","position":3,"is_corresponding":false},{"id":235855,"name":"John R. Ferdinand","orcid":"0000-0003-0936-0128","position":4,"is_corresponding":false},{"id":857791,"name":"Anaïs Portet","orcid":"0000-0001-7592-0432","position":5,"is_corresponding":false},{"id":242957,"name":"Kathleen R Bashant","orcid":"0000-0003-2868-892X","position":7,"is_corresponding":false},{"id":858426,"name":"Emeline Thevenon","orcid":null,"position":8,"is_corresponding":false},{"id":858427,"name":"Francesca Rucci","orcid":null,"position":9,"is_corresponding":false},{"id":857792,"name":"Thomas Hoyler","orcid":"0000-0003-4798-3692","position":10,"is_corresponding":false},{"id":251710,"name":"Tobias Junt","orcid":"0000-0003-0260-8346","position":11,"is_corresponding":false},{"id":218262,"name":"Mariana J. Kaplan","orcid":"0000-0003-2968-0815","position":12,"is_corresponding":false},{"id":242960,"name":"Richard M. Siegel","orcid":"0000-0001-5953-9893","position":13,"is_corresponding":false},{"id":15662,"name":"Menna R. Clatworthy","orcid":"0000-0002-3340-9828","position":14,"is_corresponding":false},{"id":15653,"name":"Nathan Richoz","orcid":"0000-0002-7422-3237","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:22:03.686498Z","pmid":"36345939","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":[]}