Incorporating mucosal-associated invariant T cells into the pathogenesis of chronic liver disease

Table 4 Mucosal-associated invariant T cells in chronic hepatitis and clinical implications

Liver disease	MAIT cell features	Clinical implications
Chronic hepatitis B	Reduced frequency circulating MAIT cells[37,38]; Depletion increased by delta infection[45]; Depleted intrahepatic MAIT cells[38,39,45]; Less granzyme B, IFN-γ, IFN-α release[36,188]; Conjugated bilirubin linked to dysfunction[39]; Increased PD-1 and CTLA-4 on MAIT cells[36]; Exhaustion correlates with HBV DNA level[36]	Chronic activation and exhaustion[36,39]; Less antiviral action[36,39,188]; Increased MAIT cell death[99]; Presumed defective protective role[36]
Chronic hepatitis C	Reduced frequency circulating MAIT cells[41,42]; Depleted intrahepatic MAIT cell[43]; Increased histologic indices reflect depletion[43]; Less TCR-activation and IFN-γ production[40,43]; Increased PD-1 and CTLA-4 on MAIT cells[41]	Hyper-activation and exhaustion[40,41,43]; Increased MAIT cell death[43,61,99]; Antiviral therapy not restorative[40,42,43]; Presumed defective protective role[43]
Alcoholic hepatitis	Reduced frequency in blood and liver[46,47,133]; Decreased granzyme B and IL-17 production[46]; Circulating bacterial products[46,47]; Increased percentage PD-1+ MAIT cells[47]; Abundant circulating stimulatory cytokines[47]; Myofibroblasts stimulated and pro-fibrotic[63]	Hyper-activation and dysfunctional[46,47]; Immune exhaustion[46,47]; Impaired intestinal mucosal barrier[46,47]; Increased MAIT cell death[47]; Diminished anti-bacterial function[133]; Presumed defective protective role[46,47]
NAFLD	Circulating MAIT cell frequency decreased[51]; Circulating cells express PD-1 and CD69[51]; Increased intrahepatic MAIT cell frequency[51]; Frequency correlates with NAFLD score[51]; Decreased IFN-γ and TNF-α production[51]; IL-4 induced polarization to M2 macrophages[51]	Activated and immune exhausted[51]; Increased hepatic migration[51]; Recruited by inflammatory activity[51]; Reduced functionality[51]; Promotes anti-inflammatory milieu[51]; Presumed defective protective role[51]
Autoimmune hepatitis	Circulating MAIT cell frequency decreased[52,53]; Reduced granzyme B and IFN-γ secretion[52,53]; Variable intrahepatic frequency[52,53]; Increased IL-17A and HSC stimulation[52]; Increased expression of PD-1 and TIM-3[52]	Activated and immune exhausted[52,53]; Reduced functionality[52,53]; Pro-inflammatory cytokine milieu[52]; Progressive fibrosis[52]; Presumed active pathogenic role[52]

CTLA-4: Cytotoxic T lymphocyte antigen 4; HBV: Hepatitis B virus; HSC: Hepatic stellate cell; IFN-α: Interferon-alpha; IFN-γ: Interferon-gamma; MAIT: Mucosal-associated invariant T; NAFLD: Non-alcoholic fatty liver disease; PD-1: Programmed cell death 1; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis; TIM-3: T cell immunoglobulin and mucin domain 3; TNF-α: Tumor necrosis factor-alpha.