{"doi":"10.1093/jimmun/vkaf283.098","title":"Myeloid heme oxygenase-1 deficiency exacerbates TLR7-induced lupus 2136","abstract":"Abstract Description Background The immunogenicity of monocytes is upregulated in systemic lupus erythematosus (SLE). However, the underlying mechanisms remain obscure. Heme oxygenase-1 (HO-1, coded by the HMOX-1 gene) is an anti-inflammatory enzyme that controls monocyte function. Compared to controls, HO-1 levels in SLE patients’ monocytes are significantly reduced. In this study, we investigated the outcomes of TLR-7-induced lupus in mice harboring HO-1 deficiency in their myeloid compartment (Hmox-1Lysm-/-). Methods Female Hmox-1Lysm-/- and littermate controls (WT) were treated epicutaneously with R848 (TLR7 agonist) for 5 weeks and outcomes were analyzed. The response of bone marrow-derived macrophages (BMDM) from both strains to R848 was compared. Results Compared to WT, Hmox-1Lysm-/- mice had significantly higher numbers of monocytes, DCs, and activated CD4+ T cells in the spleen and kidneys. Some of the cells were identified as histiocytes. The immune infiltrates in Hmox-1Lysm-/- mice had a periglomerular and interstitial distribution, but a-dsDNA IgG levels and immune complex deposits were similar between strains. R848-stimulated Hmox-1Lysm-/- BMDM had a higher expression of NFkB and produced more TNFa and IL-6 than WT cells. Conclusion A gain-of-function mutation in TLR7 or heightened TLR7 signaling is directly linked to the development of human lupus. Our data emphasizes the need for strategies to increase HO-1 in SLE myeloid cells to attenuate TLR-7-induced pathology in lupus. Funding Sources Supported by NIH (R01DK136011) to Y. Scindia and L. Morel. Vifor Pharma (P0213104) to Y. Scindia. Topic Categories Immune Mechanisms of Human Disease (HUM)","journal":"The Journal of Immunology","year":2025,"id":582511,"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":0.9589,"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":366238,"name":"Divya S. Katikaneni","orcid":"0000-0001-7562-3892","position":1,"is_corresponding":false},{"id":1494588,"name":"Norah Reedy","orcid":null,"position":2,"is_corresponding":false},{"id":1494589,"name":"Vriksha Desikan","orcid":null,"position":3,"is_corresponding":false},{"id":1300803,"name":"Tanmay Arekar","orcid":null,"position":4,"is_corresponding":false},{"id":302973,"name":"Laurence Morel","orcid":"0000-0002-6622-1290","position":5,"is_corresponding":false},{"id":442385,"name":"Yogesh Scindia","orcid":"0000-0001-6382-6289","position":6,"is_corresponding":false},{"id":1494587,"name":"Leena Al-Hraki","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:55.657290Z","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":[]}