{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:48:24Z","timestamp":1790754504106,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,4]],"date-time":"2022-12-04T00:00:00Z","timestamp":1670112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Japan Society for the Promotion of Science (JSPS)","award":["20K08893"],"award-info":[{"award-number":["20K08893"]}]},{"name":"the Japan Society for the Promotion of Science (JSPS)","award":["20K08882"],"award-info":[{"award-number":["20K08882"]}]},{"name":"the Japan Society for the Promotion of Science (JSPS)","award":["20K07809"],"award-info":[{"award-number":["20K07809"]}]},{"name":"the Japan Society for the Promotion of Science (JSPS)","award":["2020-13"],"award-info":[{"award-number":["2020-13"]}]},{"name":"the Japan Society for the Promotion of Science (JSPS)","award":["2021-07"],"award-info":[{"award-number":["2021-07"]}]},{"name":"Dokkyo Medical University, Young Investigator Award","award":["20K08893"],"award-info":[{"award-number":["20K08893"]}]},{"name":"Dokkyo Medical University, Young Investigator Award","award":["20K08882"],"award-info":[{"award-number":["20K08882"]}]},{"name":"Dokkyo Medical University, Young Investigator Award","award":["20K07809"],"award-info":[{"award-number":["20K07809"]}]},{"name":"Dokkyo Medical University, Young Investigator Award","award":["2020-13"],"award-info":[{"award-number":["2020-13"]}]},{"name":"Dokkyo Medical University, Young Investigator Award","award":["2021-07"],"award-info":[{"award-number":["2021-07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide health concern. The disease may involve immune cells including T cells, but little is known about the role(s) of the innate-like T cells in the liver. Furthermore, the most abundant innate-like T cells in the human liver are mucosal-associated invariant T (MAIT) cells, but the involvement of MAIT cells in NAFLD remains largely unexplored because of their paucity in mice. In this study, we used a novel mouse line, V\u03b119, in which the number of MAIT cells is equivalent to or greater than that in humans. Compared with the control mice, V\u03b119 mice fed a high-fat diet (HFD) exhibited a reduction in lipid accumulation, NAFLD activity score, and transcripts relevant to lipogenesis. In addition, serum triglyceride and non-esterified fatty acids were lower in V\u03b119 mice fed normal chow or HFD. In contrast, the V\u03b119 mice showed little or no change in glucose tolerance, insulin sensitivity, inflammation in adipose tissues, or intestinal permeability compared with the controls, irrespective of diet. These results suggest that the presence of MAIT cells is associated with reduced lipogenesis and lipid accumulation in the liver; however, further studies are needed to clarify the role of MAIT cells in hepatic lipid metabolism.<\/jats:p>","DOI":"10.3390\/ijms232315309","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T02:13:12Z","timestamp":1670206392000},"page":"15309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Increased Number of Mucosal-Associated Invariant T Cells Is Associated with the Inhibition of Nonalcoholic Fatty Liver Disease in High Fat Diet\u2013Fed Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Haruka","family":"Kishi","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4720-4882","authenticated-orcid":false,"given":"Isao","family":"Usui","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2907-261X","authenticated-orcid":false,"given":"Teruo","family":"Jojima","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiho","family":"Fujisaka","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Wakamatsu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuiko","family":"Mizunuma-Inoue","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Niitani","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshie","family":"Iijima","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Tomaru","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Tobe","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0610-1999","authenticated-orcid":false,"given":"Yoshimasa","family":"Aso","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sakurai, Y., Kubota, N., Yamauchi, T., and Kadowaki, T. (2021). Role of Insulin Resistance in MAFLD. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084156"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S2213-8587(22)00003-1","article-title":"A global view of the interplay between non-alcoholic fatty liver disease and diabetes","volume":"10","author":"Stefan","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/bs.acr.2020.11.001","article-title":"NAFLD-related HCC","volume":"149","author":"Banini","year":"2021","journal-title":"Adv. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nature16969","article-title":"NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis","volume":"531","author":"Ma","year":"2016","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"580968","DOI":"10.3389\/fimmu.2020.580968","article-title":"CD4(+) T Cells Mediate the Development of Liver Fibrosis in High Fat Diet-Induced NAFLD in Humanized Mice","volume":"11","author":"Her","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1001\/jama.2020.2298","article-title":"Nonalcoholic Steatohepatitis: A Review","volume":"323","author":"Sheka","year":"2020","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/nature01433","article-title":"Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1","volume":"422","author":"Treiner","year":"2003","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Martin, E., Treiner, E., Duban, L., Guerri, L., Laude, H., Toly, C., Premel, V., Devys, A., Moura, I.C., and Tilloy, F. (2009). Stepwise Development of MAIT Cells in Mouse and Human. PLoS Biol., 7.","DOI":"10.1371\/journal.pbio.1000054"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e98487","DOI":"10.1172\/jci.insight.98487","article-title":"Human MAIT cells exit peripheral tissues and recirculate via lymph in steady state conditions","volume":"3","author":"Voillet","year":"2018","journal-title":"JCI Insight"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1084\/jem.20130958","article-title":"Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells","volume":"210","author":"Reantragoon","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1002\/(SICI)1521-4141(199910)29:10<3313::AID-IMMU3313>3.0.CO;2-8","article-title":"Thymic dependence of invariant V alpha 14+ natural killer-T cell development","volume":"29","author":"Tilloy","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nature11605","article-title":"MR1 presents microbial vitamin B metabolites to MAIT cells","volume":"491","author":"Patel","year":"2012","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nature13160","article-title":"T-cell activation by transitory neo-antigens derived from distinct microbial pathways","volume":"509","author":"Corbett","year":"2014","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/cei.12277","article-title":"Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory bowel diseases","volume":"176","author":"Serriari","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1111\/jgh.13242","article-title":"MAIT cells are activated and accumulated in the inflamed mucosa of ulcerative colitis","volume":"31","author":"Haga","year":"2016","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1172\/JCI78941","article-title":"Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients","volume":"125","author":"Magalhaes","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S114","DOI":"10.1016\/j.molmet.2019.06.025","article-title":"MAIT cells in metabolic diseases","volume":"27","author":"Bertrand","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1038\/ni.3854","article-title":"Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes","volume":"18","author":"Rouxel","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1038\/s41467-020-17307-0","article-title":"Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity","volume":"11","author":"Toubal","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.jhep.2015.12.017","article-title":"Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1","volume":"64","author":"Jeffery","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1136\/gutjnl-2017-314458","article-title":"Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease","volume":"67","author":"Riva","year":"2018","journal-title":"Gut"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/hep.29782","article-title":"MAIT cells are chronically activated in patients with autoimmune liver disease and promote profibrogenic hepatic stellate cell activation","volume":"68","author":"Rombouts","year":"2018","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1038\/s41467-018-04450-y","article-title":"Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver","volume":"9","author":"Hegde","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.3389\/fimmu.2018.01994","article-title":"Mucosal-Associated Invariant T Cells Improve Nonalcoholic Fatty Liver Disease Through Regulating Macrophage Polarization","volume":"9","author":"Li","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1182\/blood-2010-08-303339","article-title":"Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17\u2013secreting T cells","volume":"117","author":"Dusseaux","year":"2011","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1084\/jem.20142110","article-title":"Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers","volume":"212","author":"Rahimpour","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e70848","DOI":"10.7554\/eLife.70848","article-title":"Reprogramming and redifferentiation of mucosal-associated invariant T cells reveal tumor inhibitory activity","volume":"11","author":"Sugimoto","year":"2022","journal-title":"eLife"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1005226","DOI":"10.3389\/fimmu.2022.1005226","article-title":"Mucosal-associated invariant T cells repress group 2 innate lymphoid cells in Alternaria alternata-induced model of allergic airway inflammation","volume":"13","author":"Shimizu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jojima, T., Wakamatsu, S., Kase, M., Iijima, T., Maejima, Y., Shimomura, K., Kogai, T., Tomaru, T., Usui, I., and Aso, Y. (2019). The SGLT2 Inhibitor Canagliflozin Prevents Carcinogenesis in a Mouse Model of Diabetes and Non-Alcoholic Steatohepatitis-Related Hepatocarcinogenesis: Association with SGLT2 Expression in Hepatocellular Carcinoma. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205237"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.4049\/jimmunol.1203218","article-title":"IL-7 Licenses Activation of Human Liver Intrasinusoidal Mucosal-Associated Invariant T Cells","volume":"190","author":"Tang","year":"2013","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/liv.13301","article-title":"Pathology of non-alcoholic fatty liver disease","volume":"37","author":"Bedossa","year":"2017","journal-title":"Liver Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.2337\/db08-1475","article-title":"Regulatory Mechanisms for Adipose Tissue M1 and M2 Macrophages in Diet-Induced Obese Mice","volume":"58","author":"Fujisaka","year":"2009","journal-title":"Diabetes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5544","DOI":"10.1038\/s41598-020-62506-w","article-title":"Bofutsushosan improves gut barrier function with a bloom of Akkermansia muciniphila and improves glucose metabolism in mice with diet-induced obesity","volume":"10","author":"Fujisaka","year":"2020","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/15309\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:33:57Z","timestamp":1760146437000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/15309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,4]]},"references-count":35,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232315309"],"URL":"https:\/\/doi.org\/10.3390\/ijms232315309","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,4]]}}}