Hepatic Immune Tolerance Induced by Hepatic Stellate Cells

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2015 Nov 18

PMID 26576077

Citations 11

Authors

Ching-Chuan Hsieh

Chien-Hui Hung

Lina Lu

Shiguang Qian

Affiliations

Soon will be listed here.

Abstract

The liver, which is a metabolic organ, plays a pivotal role in tolerance induction. Hepatic stellate cells (HpSCs), which are unique non-parenchymal cells, exert potent immunoregulatory activity during cotransplantation with allogeneic islets effectively protecting the islet allografts from rejection. Multiple mechanisms participate in the immune tolerance induced by HpSCs, including the marked expansion of myeloid-derived suppressor cells (MDSCs), attenuation of effector T cell functions and augmentation of regulatory T cells. HpSC conditioned MDSC-based immunotherapy has been conducted in mice with autoimmune disease and the results show that this technique may be promising. This article demonstrates how HpSCs orchestrate both innate immunity and adaptive immunity to build a negative network that leads to immune tolerance.

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References

Carambia A, Freund B, Schwinge D, Heine M, Laschtowitz A, Huber S . TGF-β-dependent induction of CD4⁺CD25⁺Foxp3⁺ Tregs by liver sinusoidal endothelial cells. J Hepatol. 2014; 61(3):594-9. DOI: 10.1016/j.jhep.2014.04.027. View

Schildberg F, Kurts C, Knolle P . Prominent regulatory but weak antigen-presenting cell function of hepatic stellate cells. Hepatology. 2011; 54(3):1108. DOI: 10.1002/hep.24565. View

Bhatt S, Shen G, Li Y, Qian S, Ragni M, Lu L . Hepatic stellate cell-conditioned myeloid cells provide a novel therapy for prevention of factor VIII antibody formation in mice. Exp Hematol. 2014; 43(4):277-85. DOI: 10.1016/j.exphem.2014.12.001. View

Dusabineza A, Najimi M, Van Hul N, Legry V, Khuu D, van Grunsven L . Hepatic Stellate Cells Improve Engraftment of Human Primary Hepatocytes: A Preclinical Transplantation Study in an Animal Model. Cell Transplant. 2015; 24(12):2557-71. DOI: 10.3727/096368915X686788. View

Almand B, Clark J, Nikitina E, Van Beynen J, English N, Knight S . Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 2000; 166(1):678-89. DOI: 10.4049/jimmunol.166.1.678. View

Schmielau J, Finn O . Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of t-cell function in advanced cancer patients. Cancer Res. 2001; 61(12):4756-60. View

Calne R, Sells R, Pena J, Davis D, Millard P, HERBERTSON B . Induction of immunological tolerance by porcine liver allografts. Nature. 1969; 223(5205):472-6. DOI: 10.1038/223472a0. View

Kamada N, Brons G, Davies H . Fully allogeneic liver grafting in rats induces a state of systemic nonreactivity to donor transplantation antigens. Transplantation. 1980; 29(5):429-31. DOI: 10.1097/00007890-198005000-00021. View

Giampieri M, JEZEQUEL A, Orlandi F . The lipocytes in normal human liver. A quantitative study. Digestion. 1981; 22(4):165-9. DOI: 10.1159/000198640. View

10.

Friedman S . Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies. N Engl J Med. 1993; 328(25):1828-35. DOI: 10.1056/NEJM199306243282508. View

11.

Qian S, Demetris A, Murase N, Rao A, Fung J, Starzl T . Murine liver allograft transplantation: tolerance and donor cell chimerism. Hepatology. 1994; 19(4):916-24. PMC: 2972591. DOI: 10.1002/hep.1840190418. View

12.

Lu L, Woo J, Rao A, Li Y, Watkins S, Qian S . Propagation of dendritic cell progenitors from normal mouse liver using granulocyte/macrophage colony-stimulating factor and their maturational development in the presence of type-1 collagen. J Exp Med. 1994; 179(6):1823-34. PMC: 2191530. DOI: 10.1084/jem.179.6.1823. View

13.

Lu L, Qian S, Hershberger P, Rudert W, Lynch D, Thomson A . Fas ligand (CD95L) and B7 expression on dendritic cells provide counter-regulatory signals for T cell survival and proliferation. J Immunol. 1997; 158(12):5676-84. View

14.

Bumgardner G, Heininger M, Li J, Xia D, Parker-Thornburg J, Ferguson R . A functional model of hepatocyte transplantation for in vivo immunologic studies. Transplantation. 1998; 65(1):53-61. DOI: 10.1097/00007890-199801150-00011. View

15.

Marra F, Defranco R, Grappone C, Parola M, Milani S, Leonarduzzi G . Expression of monocyte chemotactic protein-1 precedes monocyte recruitment in a rat model of acute liver injury, and is modulated by vitamin E. J Investig Med. 1999; 47(1):66-75. View

16.

Yu M, Chen C, Liang X, Wang L, Gandhi C, Fung J . Inhibition of T-cell responses by hepatic stellate cells via B7-H1-mediated T-cell apoptosis in mice. Hepatology. 2004; 40(6):1312-21. DOI: 10.1002/hep.20488. View

17.

Friedman S . Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev. 2008; 88(1):125-72. PMC: 2888531. DOI: 10.1152/physrev.00013.2007. View

18.

Chou H, Hsieh C, Charles R, Wang L, Wagner T, Fung J . Myeloid-derived suppressor cells protect islet transplants by B7-H1 mediated enhancement of T regulatory cells. Transplantation. 2011; 93(3):272-82. PMC: 3267010. DOI: 10.1097/TP.0b013e31823ffd39. View

19.

Hochst B, Schildberg F, Bottcher J, Metzger C, Huss S, Turler A . Liver sinusoidal endothelial cells contribute to CD8 T cell tolerance toward circulating carcinoembryonic antigen in mice. Hepatology. 2012; 56(5):1924-33. DOI: 10.1002/hep.25844. View

20.

Hsieh C, Chou H, Yang H, Lin F, Bhatt S, Qin J . The role of complement component 3 (C3) in differentiation of myeloid-derived suppressor cells. Blood. 2013; 121(10):1760-8. PMC: 3591797. DOI: 10.1182/blood-2012-06-440214. View