1. Figure 1 Immune mechanisms in liver homeostasis
Figure 1 | Immune mechanisms in liver homeostasis. a | The liver is constantly passaged by circulating blood cells such as monocytes, NK cells, NKT cells or T cells, which intensely interact with hepatic endothelial cells, Kupffer cells, hepatocytes and DCs. Low-level exposure to gut-derived endotoxins induces endotoxin tolerance, leading to expression of tolerogenic factors such as PD-L1, IL-10 and PGE2 by Kupffer cells and DCs. NK and NKT cells are either suppressed or programmed to exert anti-inflammatory properties, for example, by secreting IL-4. b | Interaction with adaptive lymphocytes favours induction of tolerogenic T-cell responses or deletion of autoreactive T cells. Antigen is presented by various cell types, including LSECs, liver DCs and Kupffer cells. Liver antigen-presenting cells provide cell-surface inhibitory receptors such as PD-L1 and CTLA-4 and are also dependent on cell adhesion to Kupffer cells and endothelia via ICAM-1 and VCAM-1. Furthermore, the uninflamed liver provides a tolerogenic microenvironment by the secretion of immunosuppressive factors such as IL-10, TGFβ, retinoic acid or PGE2. Ag, antigen; cDC, conventional DC; COX2, cyclooxygenase 2; CTL, cytotoxic T cell; DC, dendritic cell; FasL, Fas ligand; Flt3, Fms-like tyrosine kinase 3, GalNAc, N-acetylgalactosamine; GM-CSF, granulocyte-macrophage colony stimulating factor; HGF, hepatocyte growth factor; HMGB1, high mobility group box protein 1; HSC, hepatic stellate cell; ICAM-1, intracellular adhesion molecule; LFA, lymphocyte function associated antigen; LPS, lipopolysaccharide; LSEC, liver sinusoidal endothelial cell; MDP, muramyl dipeptide; MYD88, myeloid differentiation primary response gene 88; NK cell, natural killer cell; NKG2A, natural killer G2 receptor D; NKT cell, natural killer T cell; NLRP3, NOD-like receptor pyrin domain containing 3; NOD, nucleotide binding oligomerization domain; pDC, plasmacytoid DC; PD-L1, programmed death ligand 1; PGE2, prostaglandin E2; SMAD, small body size mothers against decapentaplegic; STAT3, signal transducer and activator of transcription; TGFβ, transforming growth factor β; TH, T helper cell; TLR, Toll-like receptor; TREG, regulatory T cell; VAP-1, vascular adhesion protein 1; VCAM-1, vascular cellular adhesion molecule; VLA4, very late antigen 4.
Heymann, F. & Tacke, F. (2016) Immunology in the liver — from homeostasis to disease
Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro