Table 1.
NK cells characteristics and activity during human and experimental NAFLD/NASH.
| Human NAFLD/NASH | Site of detection | Changes in numbers/frequency | Activation/cytotoxicity | References |
|---|---|---|---|---|
| NASH/NAFLD | Blood | Total numbers and frequencies not different. | Increased NKG2D in CD56bright/CD56dim | (34) |
| NASH obesity | Blood | Increase numbers rather than percentages. | Activated (high CD69, granzyme B) but less cytotoxic. | (35) |
| Obese | Blood | Significantly decreased NK cell levels. | NK function compromised | (36) |
| NAFLD/Fibrosis (Obese) | Blood | NK cell levels were significantly elevated in F4 subjects | Loss of tumor killing function. | (37) |
| NAFLD children (obese) | Blood | Decrease in NK cell frequency and absolute numbers | Increased activation with loss of function. Less cytotoxic (granzyme and perforin) but same IFNg |
(38) |
| Obese/insulin resistant | Blood | Lower frequency of circulating NK cells (CD3–CD56+) | Lower tumor killing capacity. Less cytotoxic function (IFN-γ) |
(39) |
| NAFLD | PBMC | Lower NK CD56dim with less NKG2D in PMBCs Liver; decreased NK56bright but increased CD56dim Fibrosis negatively correlated with liver total NKs |
Less NKG2D | (9) |
| NAFLD | liver | Decreased CD56 bright but increased CD56dim | Less NKG2D Fibrosis negatively correlated with liver total NKs | (9) |
| Obese/insulin resistant | Blood | No differences in CD56 bright and dim numbers. | Increased IL6Ra expression. Increased myeloid differentiation and inflammasome related genes | (40) |
| NAFLD | Liver | Lower cytotoxic (decreased ability to degranulate) | (41) | |
| NASH obese vs. healthy | Live | Lower numbers during NAFL Increased numbers in NASH Whereas NK cell numbers were NAFL patients revealed lower NKG2D mRNA transcription levels than patients with NASH |
Lower NKG2D mRNA in NAFL Higher NKG2D and MICA/B in NASH. | (42) |
| NAFLD/NASH Animal model | Site of detection | Changes in numbers/frequency | Activation/cytotoxicity | References |
| NASH (with weight loss) MCD (8w) | Liver | Enrichment of NK via CXLC10 | Increased activation (IFNg, TGFb IL10). Lower proliferation. | (43) |
| NAFLD (obese) High Fat/High Sugar diet (24 w) | Spleen/liver | No change in numbers | Less cytotoxic (less perforin in liver, not observed in spleen) | (41) |
| NASH (with weight loss) MCD (17 days) | Liver | No changes in frequency of DX5(+)NKp46(+) Low numbers of CD49a+NK1+ILC1 |
Increased activation (NKG2D). No changes in cytotoxicity. Polarizing Mϕ toward M1-like phenotypes via IFNg but not granzyme | (44) |
| Obese/insulin resistant HFD (16w) | Perigonadal adipose tissue | Increased NK cells numbers. | Increased IL6Ra expression. Increased myeloid differentiation/inflammation | (40) |
| Obese/insulin resistant HFD (16w) | blood | No difference in NK cells numbers. | Increased IL6Ra expression. Increased myeloid differentiation/inflammation | (40) |
| Obese/insulin resistant HFD (16w) | liver | No difference in NK cells numbers. | Increased IL6Ra expression. Increased myeloid differentiation/inflammation | (40) |
| Obese db/db mice (Leptin receptor KOs) | Blood, spleen, liver and lung | Decreased numbers and percentage | Less cytotoxic (leptin dependent). | (45) |
| NAFLD IL15 KO mice on HFD (16w) | Liver | Increased numbers on HFD but frequency comparable WT vs KO | IL15 KO have lower chemokine production. | (46) |
| Spontaneous NASH GNMT KO mice |
Liver/Spleen | Decreased numbers | More cytotoxic, more activated with high TRAIL expression. | (47) |