{"doi":"10.1002/eji.202350474","title":"Invariant natural killer T cells drive hepatic homeostasis in nonalcoholic fatty liver disease via sustained IL‐10 expression in CD170<sup>+</sup> Kupffer cells","abstract":"Kupffer cells (KCs) are liver-resident macrophages involved in hepatic inflammatory responses, including nonalcoholic fatty liver disease (NAFLD) development. However, the contribution of KC subsets to liver inflammation remains unclear. Here, using high-dimensional single-cell RNA sequencing, we characterized murine embryo-derived KCs and identified two KC populations with different gene expression profiles: KC-1 and KC-2. KC-1 expressed CD170, exhibiting immunoreactivity and immune-regulatory abilities, while KC-2 highly expressed lipid metabolism-associated genes. In a high-fat diet-induced NAFLD model, KC-1 cells differentiated into pro-inflammatory phenotypes and initiated more frequent communications with invariant natural killer T (iNKT) cells. In KC-1, interleukin (IL)-10 expression was unaffected by the high-fat diet but impaired by iNKT cell ablation and upregulated by iNKT cell adoptive transfer in vivo. Moreover, in a cellular co-culture system, primary hepatic iNKT cells promoted IL-10 expression in RAW264.7 and primary KC-1 cells. CD206 signal blocking in KC-1 or CD206 knockdown in RAW264.7 cells significantly reduced IL-10 expression. In conclusion, we identified two embryo-derived KC subpopulations with distinct transcriptional profiles. The CD206-mediated crosstalk between iNKT and KC-1 cells maintains IL-10 expression in KC-1 cells, affecting hepatic immune balance. Therefore, KC-based therapeutic strategies must consider cellular heterogeneity and the local immune microenvironment for enhanced specificity and efficiency.","journal":"European Journal of Immunology","year":2023,"id":349849,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9456,"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":1093376,"name":"Jinke Geng","orcid":"0000-0002-2156-6367","position":1,"is_corresponding":false},{"id":1093377,"name":"Shuangshuang Zhang","orcid":"0009-0000-2944-4615","position":2,"is_corresponding":false},{"id":475646,"name":"Jia Rao","orcid":"0000-0003-2839-3419","position":3,"is_corresponding":false},{"id":733869,"name":"Yansong Zhu","orcid":"0000-0002-3877-9369","position":4,"is_corresponding":false},{"id":960136,"name":"Shaodong Xu","orcid":null,"position":5,"is_corresponding":false},{"id":1093378,"name":"Fei Wang","orcid":"0000-0002-5676-2181","position":6,"is_corresponding":false},{"id":1093379,"name":"Fang Ma","orcid":"0009-0008-5339-9349","position":7,"is_corresponding":false},{"id":1093380,"name":"Zhou Meng","orcid":"0009-0009-9781-883X","position":8,"is_corresponding":false},{"id":863185,"name":"Hong Zhou","orcid":"0000-0003-0120-3347","position":9,"is_corresponding":false},{"id":1093375,"name":"Mutian Han","orcid":"0000-0002-2456-4893","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T01:12:19.059218Z","pmid":"37489253","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":[]}