Table 2.

The major findings related to NKT cells and liver fibrosis

The references	Models	Major findings	Suggested functions
de Lalla et al. [52] 2004	Analyses of circulating and liver iNKT in HCV patients	iNKT cells were increased in chronically HBV- or HCV-infected livers with preferential production of profibrotic IL-4 and IL-13 cytokines. In vitro CD1d-dependent activation of iNKT cells from healthy donors elicited IL-4 and IL-13.	Pro-fibrotic
Park et al. [53] 2009	CCl4 treatment in mice	Jα18 KO mice had a higher grade of fibrosis than WT mice at 2 weeks, but not 4 weeks, after CCl4 injection. Administration of the iNKT activator α-GalCer accelerated CCl4-induced acute liver injury and fibrosis but had no effects in the chronic model. Incubation with NKT cells killed HSCs in vitro.	Pro-fibrotic Anti-fibrotic
Miyagi et al. [66] 2010	Mouse model (HFD feeding)	Jα18 KO mice were more susceptible to HFD-induced inflammation and fibrosis (on a BALB/c background).	Anti-fibrotic
Syn et al. [63] 2010	Mouse model (MCD feeding); Human NASH cirrhotic livers	NASH cirrhotic livers had higher numbers of NKT cells compared to healthy livers. Patched-deficient mice with an accumulation of liver NKT cells had increased liver fibrosis, while CD1d KO mice had decreased liver fibrosis in a model of MCD feeding.	Pro-fibrotic
Jin et al. [68] 2011	Mouse model (HBV TG mice)	NKT cells were over-activated in chronic CCl4-treated HBV TG mice. Depletion of NKT cells reduced, while adaptive transfer of NKT cells enhanced, CCl4-induced liver injury and fibrosis.	Pro-fibrotic
Ishikawa et al. [54] 2011	Mouse model (chronic TAA injection)	CD1d KO mice had decreased liver inflammation, injury, and fibrosis compared to WT mice after TAA administration.	Pro-fibrotic
Syn et al. [67] 2012	Mouse model (MCD diet feeding)	Jα18 KO and CD1d KO mice had significantly reduced hedgehog and osteopontin expression and less fibrosis compared to WT mice in a model of MCD diet feeding.	Pro-fibrotic