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An accumulation of fat, followed by inflammation, is the major cause of NAFLD progression. During inflammation, macrophages are the most abundant immune cells recruited to the site of injury. Macrophages are classified into \u201cproinflammatory\u201d M1 macrophages, and \u201canti-inflammatory\u201d M2 macrophages. In NAFLD, M1 macrophages are the most prominent macrophages that lead to an excessive inflammatory response. Previously, we found that baicalin could polarize macrophages into anti-inflammatory M2c subtype macrophages with an increased level of MERTK expression. Several studies have also shown a strong correlation between MERTK expression and cholesterol efflux, efferocytosis, as well as phagocytosis capability. Therefore, in this study, we aim to elucidate the potential and efficacy of mononuclear-cell (MNC)-derived MERTK+\/hi M2c macrophages induced by baicalin as a cell-based therapy for NAFLD treatment. In our results, we have demonstrated that a MERTK+\/hi M2c macrophage injection to NAFLD mice contributes to an increased level of serum HDL secretion in the liver, a decline in the circulating CD4+CD25\u2212 and CD8+CD25\u2212 T cells and lowers the total NAFLD pathological score by lessening the inflammation, necrosis, and fibrosis. In the liver, profibrotic COL1A1 and FN, proinflammation TNF\u03b1, as well as the regulator of lipid metabolism PPAR\u0263 expression, were also downregulated after injection. In parallel, the transcriptomic profiles of the injected MERTK+\/hi M2c macrophages showed that the various genes directly or indirectly involved in NAFLD progression (e.g., SERPINE1, FADS2) were also suppressed. Downregulation of cytokines and inflammation-associated genes, such as CCR5, may promote a pro-resolving milieu in the NAFLD liver. Altogether, cell-based therapy using MERTK+\/hi M2c macrophages is promising, as it ameliorates NAFLD in mice.<\/jats:p>","DOI":"10.3390\/ijms221910604","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T10:22:42Z","timestamp":1632997362000},"page":"10604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["MERTK+\/hi M2c Macrophages Induced by Baicalin Alleviate Non-Alcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"22","author":[{"family":"Junior","sequence":"first","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-9038","authenticated-orcid":false,"given":"Yin-Siew","family":"Lai","sequence":"additional","affiliation":[{"name":"Research Center for Animal Biologics, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huyen Thi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farrah P.","family":"Salmanida","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9383-831X","authenticated-orcid":false,"given":"Ko-Tung","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"},{"name":"Research Center for Animal Biologics, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"},{"name":"Flow Cytometry Center, Precision Instruments Center, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver, and European Association for the Study of Diabetes (EASD) (2016). 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