Nonalcoholic fatty liver disease (
NAFLD) is one of the most common
liver diseases worldwide. 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 "proinflammatory" M1 macrophages, and "anti-inflammatory" 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- and CD8+CD25- T cells and lowers the total
NAFLD pathological score by lessening the
inflammation,
necrosis, and
fibrosis. In the liver, profibrotic COL1A1 and FN, proinflammation TNFα, as well as the regulator of lipid metabolism PPARɣ 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.