{"doi":"10.1126/sciimmunol.add1599","title":"NKG2D-mediated detection of metabolically stressed hepatocytes by innate-like T cells is essential for initiation of NASH and fibrosis","abstract":"Metabolic-associated fatty liver disease (MAFLD) is a spectrum of clinical manifestations ranging from benign steatosis to cirrhosis. A key event in the pathophysiology of MAFLD is the development of nonalcoholic steatohepatitis (NASH), which can potentially lead to fibrosis and hepatocellular carcinoma, but the triggers of MAFLD-associated inflammation are not well understood. We have observed that lipid accumulation in hepatocytes induces expression of ligands specific to the activating immune receptor NKG2D. Tissue-resident innate-like T cells, most notably γδ T cells, are activated through NKG2D and secrete IL-17A. IL-17A licenses hepatocytes to produce chemokines that recruit proinflammatory cells into the liver, which causes NASH and fibrosis. NKG2D-deficient mice did not develop fibrosis in dietary models of NASH and had a decreased incidence of hepatic tumors. The frequency of IL-17A + γδ T cells in the blood of patients with MAFLD correlated directly with liver pathology. Our findings identify a key molecular mechanism through which stressed hepatocytes trigger inflammation in the context of MAFLD.","journal":"Science Immunology","year":2023,"id":321276,"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":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"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":1033288,"name":"Maja Lenartić","orcid":"0000-0003-4702-7115","position":1,"is_corresponding":false},{"id":1033289,"name":"Karlo Mladenić","orcid":"0000-0002-8056-0969","position":2,"is_corresponding":false},{"id":1033290,"name":"Marko Šestan","orcid":"0000-0002-1473-6647","position":3,"is_corresponding":false},{"id":1033291,"name":"Inga Kavazović","orcid":"0000-0003-4704-6199","position":4,"is_corresponding":false},{"id":1033292,"name":"Ante Benić","orcid":"0000-0003-1061-3188","position":5,"is_corresponding":false},{"id":1033293,"name":"Mia Krapić","orcid":"0000-0002-4133-7000","position":6,"is_corresponding":false},{"id":1033294,"name":"Lukas Rindlisbacher","orcid":"0000-0002-9408-1336","position":7,"is_corresponding":false},{"id":657166,"name":"Maja Cokarić Brdovčak","orcid":"0000-0002-9335-8700","position":8,"is_corresponding":false},{"id":1033295,"name":"Colin Sparano","orcid":"0000-0003-0776-6896","position":9,"is_corresponding":false},{"id":1033955,"name":"Gioana Litscher","orcid":null,"position":10,"is_corresponding":false},{"id":1033296,"name":"Tamara Turk Wensveen","orcid":"0000-0003-3813-1535","position":11,"is_corresponding":false},{"id":1033297,"name":"Ivana Mikolašević","orcid":"0000-0001-9676-0642","position":12,"is_corresponding":false},{"id":1033298,"name":"Dora Fučkar Čupić","orcid":"0000-0001-6909-1631","position":13,"is_corresponding":false},{"id":1033299,"name":"Lidija Bilić-Zulle","orcid":"0000-0002-4497-6457","position":14,"is_corresponding":false},{"id":1033956,"name":"Aleksander Steinle","orcid":null,"position":15,"is_corresponding":false},{"id":297384,"name":"Ari Waisman","orcid":"0000-0003-4304-8234","position":16,"is_corresponding":false},{"id":312634,"name":"Adrian Hayday","orcid":"0000-0002-9495-5793","position":17,"is_corresponding":false},{"id":1033300,"name":"Sònia Tugues","orcid":"0000-0003-1206-3386","position":18,"is_corresponding":false},{"id":65555,"name":"Burkhard Becher","orcid":"0000-0002-1541-7867","position":19,"is_corresponding":false},{"id":1033301,"name":"Bojan Polić","orcid":"0000-0003-3930-9630","position":20,"is_corresponding":false},{"id":1033302,"name":"Felix M. Wensveen","orcid":"0000-0002-1333-8882","position":21,"is_corresponding":false},{"id":1033287,"name":"Sonja Marinović","orcid":"0000-0002-4054-338X","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T01:07:32.611759Z","pmid":"37774007","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":[]}