Liver infiltrating T cells regulate bile acid metabolism in experimental cholangitis

Glaser, Fabian; John, Clara; Engel, Bastian; Höh, Benedikt; Weidemann, Sören; Dieckhoff, Jan; Stein, Stephanie; Becker, Nathalie; Casar, Christian; Schuran, Fenja Amrei; Wieschendorf, Björn; Preti, Max; Jessen, Friederike; Franke, André; Carambia, Antonella; Lohse, Ansgar W.; Ittrich, Harald; Herkel, Johannes; Heeren, Joerg; Schramm, Christoph; Schwinge, Dorothee

doi:10.1016/j.jhep.2019.05.030

Cited by 33 publications

(28 citation statements)

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“…Liver, a central detoxifying organ of the body, is also the primary organ regulating gluconeogenesis and lipogenesis (Glaser et al., 2019; Liu et al., 2013; Sunny, Parks, Browning, & Burgess, 2011). The disturbance in intra‐hepatic lipid homeostasis has emerged as a risk factor for the development of liver diseases, such as fat liver and non‐alcoholic steatohepatitis, leading to retarded growth in human and animals (Bechmann et al., 2012; Liu et al., 2013; Mohamed, Sarhan, Eladl, El‐Remessy, & El‐Sherbiny, 2018).…”

Section: Discussionmentioning

confidence: 99%

Effects of dietary fibres on gut microbial metabolites and liver lipid metabolism in growing pigs

Chen

et al. 2020

Animal Physiology Nutrition

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This study was conducted to investigate the effects of dietary supplementation with wheat bran fibre, inulin and their combination on growth performance, short‐chain fatty acids (SCFAs) production in caecum and colon and liver lipid metabolism in growing pigs. A total of 48 Duroc × Landrace × Yorkshire cross‐bred growing pigs (73 ± 2 days of age; 24.37 ± 2.86 kg) were allocated to four groups randomly, each group consisting of six pens with two pigs each. The pigs were fed a control diet (CON), a diet containing 2% wheat bran fibre (WB), a diet containing 2% inulin (IN), and a diet containing both of 1% wheat bran fibre and 1% inulin (MIX), respectively. The trial lasted for 28 days. The results showed that MIX fed pigs had a higher percentage of fat in the liver than those fed the CON (p < .05). IN, WB or MIX feeding decreased the concentrations of acetate and total SCFAs in colon compared with CON (p < .01). Feeding WB or IN also decreased the colonic butyrate concentrations compared with CON (p < .01). However, the serum level of valeric acid was elevated in the IN, WB and MIX group (p < .01). MIX fed pigs tended to have lower levels of propionate in serum than the WB fed pigs (p = .098). MIX feeding enhanced the mRNA expression of lipid synthesis‐related genes in liver compared with CON (p < .05). Feeding IN decreased the expression of bile acids synthesis‐related genes in liver and increased mRNA expression of SCFAs transporter SLC16A1 in colon compared with CON (p < .05). In this study, these data indicated that the combined supplementation of wheat bran fibre and inulin decreased the SCFAs concentrations in the colon, enhanced the genes FAS and HNF‐4α mRNA expression in liver and induced liver lipid accumulation in growing pigs.

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Section: Discussionmentioning

confidence: 99%

Effects of dietary fibres on gut microbial metabolites and liver lipid metabolism in growing pigs

Chen

et al. 2020

Animal Physiology Nutrition

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“…Bile acid synthesis by cholangiocytes is modulated by inflammatory T cells Direct antigen presentation by cholangiocytes to T cells in an MHC-restricted fashion can also lead to biliary injury. 219,220 Transgenic overexpression of ovalbumin in cholangiocytes (ASBT-OVA) preferentially activates OVA-specific CD8 + T cells but not CD4 + T cells, leading to liver injury. 219 Additionally, adoptive transfer of antigen-specific CD8 + T cells into Mdr2 -/-xK14-OVAp mice, which express the OVA peptide in cholangiocytes, is sufficient to induce biliary disease.…”

Section: Cholangiocytes As Nonconventional Antigen-presenting Cellsmentioning

confidence: 99%

“…219 Additionally, adoptive transfer of antigen-specific CD8 + T cells into Mdr2 -/-xK14-OVAp mice, which express the OVA peptide in cholangiocytes, is sufficient to induce biliary disease. 220 Antigen-specific CD8 + T cells localized in the peribiliary regions and were associated with the downregulation of enzymes involved in bile acid (BA) synthesis (cholesterol 7α-hydroxylase (Cyp7a1), sterol 12αhydroxylase (Cyp8b1), sterol 27α -hydroxylase (Cyp27a1), and oxysterol-7α hydroxylase (Cyp7b1)) and an increase in BA secretion by HCs. Blocking IFNγ and TNFα with antibodies resulted in the upregulation of key enzymes involved in BA synthesis (Cyp7a1/Cyp8b1) and BA transporters, 220 indicating that this change in BA synthesis depended on inflammatory cytokines and the presence of inflammatory CD8 + T cells.…”

Section: Cholangiocytes As Nonconventional Antigen-presenting Cellsmentioning

confidence: 99%

“…220 Antigen-specific CD8 + T cells localized in the peribiliary regions and were associated with the downregulation of enzymes involved in bile acid (BA) synthesis (cholesterol 7α-hydroxylase (Cyp7a1), sterol 12αhydroxylase (Cyp8b1), sterol 27α -hydroxylase (Cyp27a1), and oxysterol-7α hydroxylase (Cyp7b1)) and an increase in BA secretion by HCs. Blocking IFNγ and TNFα with antibodies resulted in the upregulation of key enzymes involved in BA synthesis (Cyp7a1/Cyp8b1) and BA transporters, 220 indicating that this change in BA synthesis depended on inflammatory cytokines and the presence of inflammatory CD8 + T cells. These data indicate that there is bidirectional communication between biliary APCs and inflammatory T cells that can influence BA metabolism.…”

Section: Cholangiocytes As Nonconventional Antigen-presenting Cellsmentioning

confidence: 99%

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Antigen presentation, autoantibody production, and therapeutic targets in autoimmune liver disease

et al. 2020

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The liver is an important immunological organ that controls systemic tolerance. The liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and maintenance. Orchestrating the immune response in homeostasis depends on a healthy and well-toned immunological liver microenvironment, which is maintained by the crosstalk of liver-resident antigen-presenting cells and intrahepatic and liver-infiltrating leukocytes. In response to pathogens or autoantigens, tolerance is disrupted by unknown mechanisms. Intrahepatic parenchymal and nonparenchymal cells exhibit unique antigen-presenting properties. The presentation of microbial and endogenous lipid-, metabolite- and peptide-derived antigens from the gut via conventional and nonconventional mechanisms can educate intrahepatic immune cells and elicit effector responses or tolerance. Perturbation of this balance results in autoimmune liver diseases, such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Although the exact etiologies of these autoimmune liver diseases are unknown, it is thought that the disruption of tolerance towards self-antigens and microbial metabolites and lipids, as well as alterations in bile acid composition, may result in changes in effector cell activation and polarization and may reduce or impair protective anti-inflammatory regulatory T and B cell responses. Additionally, the canonical and noncanonical transmission of antigens and antigen:MHC complexes via trogocytosis or extracellular vesicles between different (non) immune cells in the liver may play a role in the induction of hepatic inflammation and tolerance. Here, we summarize emerging aspects of antigen presentation, autoantibody production, and the application of novel therapeutic approaches in the characterization and treatment of autoimmune liver diseases.

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“…Therefore, a better understanding of the contribution of bile acid accumulation and metabolism to inflammation might well provide novel therapeutic targets. In this edition of the Journal of Hepatology, Glaser et al 16…”

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confidence: 99%

Bile acid metabolism and T cell responses in cholangiopathy: Not one-way traffic

Shetty

Boyer

2019

Journal of Hepatology

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Liver infiltrating T cells regulate bile acid metabolism in experimental cholangitis

Cited by 33 publications

References 50 publications

Effects of dietary fibres on gut microbial metabolites and liver lipid metabolism in growing pigs

Effects of dietary fibres on gut microbial metabolites and liver lipid metabolism in growing pigs

Antigen presentation, autoantibody production, and therapeutic targets in autoimmune liver disease

Bile acid metabolism and T cell responses in cholangiopathy: Not one-way traffic

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