{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T05:35:31Z","timestamp":1792992931774,"version":"4.5.0"},"reference-count":0,"publisher":"The Korean Association for the Study of the Liver","issue":"4","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":["e-cmh.org"],"crossmark-restriction":true},"short-container-title":["Clin Mol Hepatol"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"Background\/Aims: Bone marrow mesenchymal stromal cells (BM-MSCs) exert diverse functions, including supporting alcohol detoxification and providing a niche for monocyte development. However, their role in regulating monocytes during alcohol-associated liver disease (ALD) remains unclear. This study investigates how BM-MSCs orchestrate the egress of anti-inflammatory monocytes from BM to the liver in ALD.Methods: Wild-type, leptin receptor (LepR)\u207a BM-MSC-specific <i>Slc7a11<\/i> knockout, and natural killer (NK) cell-specific <i>Grm5<\/i> knockout mice were fed an ethanol diet for 8 weeks. Tissue analyses were performed using single-cell RNA sequencing (scRNA-seq), immunostaining, and flow cytometry. Blood and liver samples from ALD patients were examined.Results: scRNA-seq revealed a distinct population of BM-derived Ly6C<sup>low<\/sup> hepatic macrophages expressing interleukin-1 receptor 2 (IL-1R2), an IL-1\u03b2 decoy receptor, in ethanol-fed mice. In the BM, alcohol exposure upregulated the gene expression of alcohol-metabolizing enzymes (<i>Adh1, Aldh2<\/i>), xCT (<i>Slc7a11<\/i>), and chemokines (<i>Cxcl9, Cxcl10<\/i>) in LepR<sup>+<\/sup> BM-MSCs, promoting NK cell recruitment and interferon-\u03b3 (IFN-\u03b3) production via metabotropic glutamate receptor 5 (mGluR5) activation. Subsequently, IFN-\u03b3 enhanced IL-1R2 expression and suppressed CX<sub>3<\/sub>CR1 in neighboring Ly6C<sup>low<\/sup> BM monocytes, facilitating their hepatic migration. LepR<sup>+<\/sup> BM-MSC-specific xCT and NK cell-specific mGluR5 knockout mice exhibited exacerbated liver injury and elevated blood IL-1\u03b2 levels, while recombinant IL-1R2 administration ameliorated ALD in wild-type mice. Consistently, increased IL-1R2 levels were observed in plasma, CD14<sup>+<\/sup>CD16<sup>+<\/sup> blood monocytes, and liver tissues of ALD patients.Conclusions: We identified a BM-liver axis in which glutamate released by BM-MSCs activates mGluR5 in BM NK cells, driving IL-1R2<sup>+<\/sup> monocyte migration to the liver and attenuating ALD progression.<\/jats:p>","DOI":"10.3350\/cmh.2026.0425","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T23:53:31Z","timestamp":1781826811000},"page":"e2026.0425","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glutamate excreted by leptin receptor+ bone marrow mesenchymal stromal cells mitigates alcohol-associated liver disease by promoting interleukin-1 receptor 2+ monocyte migration"],"prefix":"10.3350","volume":"32","author":[{"given":"Young-Ri","family":"Shim","sequence":"first","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"},{"name":"Department of Pathology, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"},{"name":"Department of Pathology, Yale School of Medicine, New Haven, CT, USA"},{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"},{"name":"Department of Surgery, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyurae","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Eun","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine Po Sin","family":"Chung","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunmi","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihyo","family":"Byun","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewoo","family":"Oh","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Min","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Ho","family":"Byun","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Single-Cell Medical Genomics Laboratory, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6396-0859","authenticated-orcid":true,"given":"Young-Sun","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"},{"name":"Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4240-4631","authenticated-orcid":true,"given":"Won-Il","family":"Jeong","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea"},{"name":"Center for the Hepatic Glutamate and Its Function, KAIST, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1902","container-title":["Clinical and Molecular Hepatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-cmh.org\/upload\/pdf\/cmh-2026-0425.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-cmh.org\/journal\/view.php?doi=10.3350\/cmh.2026.0425","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-cmh.org\/upload\/pdf\/cmh-2026-0425.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T05:02:42Z","timestamp":1792990962000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-cmh.org\/journal\/view.php?doi=10.3350\/cmh.2026.0425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"URL":"https:\/\/doi.org\/10.3350\/cmh.2026.0425","relation":{},"ISSN":["2287-2728","2287-285X"],"issn-type":[{"value":"2287-2728","type":"print"},{"value":"2287-285X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"assertion":[{"value":"2026-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-18","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-01","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}