1. Nat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2015.200
Figure 2 Molecular signals triggering inflammatory immune activation in the liver
Figure 2 | Molecular signals triggering inflammatory immune activation in the liver. Dependent on the underlying type of injury or disease, different alarmins, danger signals such as ATP, HMGB1, cholesterol or FFAs are released, especially by hepatocytes and also Kupffer cells. These signals, in conjunction with extrahepatic signals such as LPS or complement, promote further inflammatory activation (e.g. inflammasome activation via TLR4) of HSCs and Kupffer cells and endothelia, followed by an expression of adhesion molecules such as E-Selectin, ICAM-1, VCAM-1 and VAP-1, which is commonly observed in virtually all liver diseases. Hepatocytes, LSECs, HSCs and Kupffer cells release inflammatory chemokines and inflammatory cytokines (e.g. IL1-β, IL-18, TNF, IL-6) leading to subsequent attraction and activation of circulating immune cells. Please note that several mechanisms such as activation of complement and the inflammasome NLRP3 as well as TLR-mediated pattern recognition are conserved throughout different disease types. ALD, alcoholic liver disease; CB, cannabinoid receptor; CLD, chronic liver disease; CRP, C-reactive protein; DC, dendritic cell; FFA, free fatty acid; HMGB1, high mobility group box protein 1; HSC, hepatic stellate cell; ICAM-1, intracellular adhesion molecule; LPS, lipopolysaccharide; LTA, lymphotoxin-α; MBL, mannan binding lectin; MYD88, myeloid differentiation primary response gene 88; NLRP3, NOD-like receptor pyrin domain containing 3; PDGF, platelet-derived growth factor; TLR, Toll-like receptor; TRIF, TIR domain containing adaptor inducing interferon-β; TGFβ, transforming growth factor β; α-SMA, alpha smooth muscle actin; VAP-1, vascular adhesion protein 1; VCAM-1, vascular cellular adhesion molecule; VEGF, vascular endothelial growth factor.
Heymann, F. & Tacke, F. (2016) Immunology in the liver — from homeostasis to disease
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