Research advances in the role of the glucocorticoid-induced tumor necrosis factor receptor-related protein and its ligand in liver diseases

Yu HE; Jidong JIA; Ping WANG

doi:10.3969/j.issn.1001-5256.2021.07.051

Volume 37 Issue 7

Jul. 2021

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Article Navigation > Journal of Clinical Hepatology > 2021 > 37(7): 1718-1723

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Research advances in the role of the glucocorticoid-induced tumor necrosis factor receptor-related protein and its ligand in liver diseases

DOI: 10.3969/j.issn.1001-5256.2021.07.051

Yu HE^a,
Jidong JIA^{a, b},
Ping WANG^{a
,
,}

a.
Liver Disease Center, Beijing Friendship Hospital, Capital Medical University; Beijing 100050, China
b.
Beijing Clinical Institute, Beijing Friendship Hospital, Capital Medical University; Beijing 100050, China

Research funding:

Chinese Foundation for Hepatitis Prevention and Control of the Wcay Baoen Liver Fibrosis Foundation (2019073);

National Science and Technology Major Special Project for New Drug Development (2018ZX09201016)

Received Date: 2020-12-24
Accepted Date: 2021-02-15
Published Date: 2021-07-20

Abstract

Abstract

Glucocorticoid-induced tumor necrosis factor receptor (GITR) is a member of the tumor necrosis factor receptor superfamily, and after it specifically binds to GITR ligand (GITRL), the downstream signals mediated by them can not only serve as a costimulatory molecule to promote the proliferation and cytokine secretion of effector T cells, but also affect the proliferation of regulatory T cells and inhibit the function of effector T cells, thereby regulating the inflammatory response and tumor cell-killing effect of effector T cells. GITRL is mainly expressed in antigen- presenting cells and has an intracellular domain, and the binding of GITRL to GITR can affect the function of antigen-presenting cells via receptor/ligand reverse signaling. In liver diseases, GITRL/GITR signal is not only involved in immune rejection after liver transplantation and gene therapy, but also associated with the formation of tumor immune microenvironment and the immune escape of tumor. Further studies are needed to explore the role of GITRL/GITR in the development and progression of other liver diseases.
- Liver Diseases,
- Glucocorticoid-Induced TNFR-Related Protein,
- Glucocorticoid-Induced TNFR-Related Ligand,
- Immunomodulation,
- T-Lymphocytes, Regulatory

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References

[1]	NOCENTINI G, GIUNCHI L, RONCHETTI S, et al. A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis[J]. Proc Natl Acad Sci U S A, 1997, 94(12): 6216-6221. DOI: 10.1073/pnas.94.12.6216.
[2]	GURNEY AL, MARSTERS SA, HUANG RM, et al. Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR[J]. Curr Biol, 1999, 9(4): 215-218. DOI: 10.1016/s0960-9822(99)80093-1.
[3]	KIM JD, CHOI BK, BAE JS, et al. Cloning and characterization of GITR ligand[J]. Genes Immun, 2003, 4(8): 564-569. DOI: 10.1038 /sj.gene.6364026.
[4]	NOCENTINI G, RICCARDI C. GITR: A modulator of immune response and inflammation[J]. Adv Exp Med Biol, 2009, 647: 156-173. DOI: 10.1007/978-0-387-89520-8_11.
[5]	RICCARDI C, RONCHETTI S, NOCENTINI G. Glucocorticoid-induced TNFR-related gene (GITR) as a therapeutic target for immunotherapy[J]. Expert Opin Ther Targets, 2018, 22(9): 783-797. DOI: 10.1080/14728222.2018.1512588.
[6]	SHIMIZU J, YAMAZAKI S, TAKAHASHI T, et al. Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance[J]. Nat Immunol, 2002, 3(2): 135-142. DOI: 10.1038/ni759.
[7]	KOHM AP, PODOJIL JR, WILLIAMS JS, et al. CD28 regulates glucocorticoid-induced TNF receptor family-related gene expression on CD4⁺ T cells via IL-2-dependent mechanisms[J]. Cell Immunol, 2005, 235(1): 56-64. DOI: 10.1016/j.cellimm.2005.07.002.
[8]	RONCHETTI S, ZOLLO O, BRUSCOLI S, et al. GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations[J]. Eur J Immunol, 2004, 34(3): 613-622. DOI: 10.1002/eji.200324804.
[9]	KOHM AP, WILLIAMS JS, MILLER SD. Cutting edge: Ligation of the glucocorticoid-induced TNF receptor enhances autoreactive CD4⁺ T cell activation and experimental autoimmune encephalomyelitis[J]. J Immunol, 2004, 172(8): 4686-4690. DOI: 10.4049/jimmunol.172.8.4686.
[10]	van OLFFEN RW, KONING N, van GISBERGEN KP, et al. GITR triggering induces expansion of both effector and regulatory CD4⁺ T cells in vivo[J]. J Immunol, 2009, 182(12): 7490-7500. DOI: 10.4049/jimmunol.0802751.
[11]	RONCHETTI S, NOCENTINI G, BIANCHINI R, et al. Glucocorticoid-induced TNFR-related protein lowers the threshold of CD28 costimulation in CD8⁺ T cells[J]. J Immunol, 2007, 179(9): 5916-5926. DOI: 10.4049/jimmunol.179.9.5916.
[12]	SNELL LM, MCPHERSON AJ, LIN GH, et al. CD8 T cell-intrinsic GITR is required for T cell clonal expansion and mouse survival following severe influenza infection[J]. J Immunol, 2010, 185(12): 7223-7234. DOI: 10.4049/jimmunol.0903080.
[13]	PEDROZA-GONZALEZ A, ZHOU G, SINGH SP, et al. GITR engagement in combination with CTLA-4 blockade completely abrogates immunosuppression mediated by human liver tumor-derived regulatory T cells ex vivo[J]. Oncoimmunology, 2015, 4(12): e1051297. DOI: 10.1080/2162402X.2015.1051297.
[14]	VENCE L, BUCKTROUT SL, FERNANDEZ CURBELO I, et al. Characterization and comparison of GITR expression in solid tumors[J]. Clin Cancer Res, 2019, 25(21): 6501-6510. DOI: 10.1158/1078-0432.CCR-19-0289.
[15]	NOWAKOWSKA DJ, KISSLER S. Ptpn22 modifies regulatory T cell homeostasis via GITR upregulation[J]. J Immunol, 2016, 196(5): 2145-2152. DOI: 10.4049/jimmunol.1501877.
[16]	MAHMUD SA, MANLOVE LS, SCHMITZ HM, et al. Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T cells[J]. Nat Immunol, 2014, 15(5): 473-481. DOI: 10.1038/ni.2849.
[17]	TIAN J, ZHANG B, RUI K, et al. The role of GITR/GITRL interaction in autoimmune diseases[J]. Front Immunol, 2020, 11: 588682. DOI: 10.3389/fimmu.2020.588682.
[18]	CARRIER Y, WHITTERS MJ, MIYASHIRO JS, et al. Enhanced GITR/GITRL interactions augment IL-27 expression and induce IL-10-producing Tr-1 like cells[J]. Eur J Immunol, 2012, 42(6): 1393-1404. DOI: 10.1002/eji.201142162.
[19]	WANG S, SHI Y, YANG M, et al. Glucocorticoid-induced tumor necrosis factor receptor family-related protein exacerbates collagen-induced arthritis by enhancing the expansion of Th17 cells[J]. Am J Pathol, 2012, 180(3): 1059-1067. DOI: 10.1016/j.ajpath.2011.11.018.
[20]	KO K, YAMAZAKI S, NAKAMURA K, et al. Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3⁺CD25⁺CD4⁺ regulatory T cells[J]. J Exp Med, 2005, 202(7): 885-891. DOI: 10.1084/jem.20050940.
[21]	SUKUMAR S, WILSON DC, YU Y, et al. Characterization of MK-4166, a clinical agonistic antibody that targets human GITR and inhibits the generation and suppressive effects of t regulatory cells[J]. Cancer Res, 2017, 77(16): 4378-4388. DOI: 10.1158/0008-5472.CAN-16-1439.
[22]	MA J, FENG D, WEI Y, et al. Blockade of glucocorticoid-induced tumor necrosis factor-receptor-related protein signaling ameliorates murine collagen-induced arthritis by modulating follicular helper T cells[J]. Am J Pathol, 2016, 186(6): 1559-1567. DOI: 10.1016/j.ajpath.2016.02.010.
[23]	OJA AE, BRASSER G, SLOT E, et al. GITR shapes humoral immunity by controlling the balance between follicular T helper cells and regulatory T follicular cells[J]. Immunol Lett, 2020, 222: 73-79. DOI: 10.1016/j.imlet.2020.03.008.
[24]	PEDROS C, ALTMAN A, KONG KF. Role of TRAFs in signaling pathways controlling T follicular helper cell differentiation and T cell-dependent antibody responses[J]. Front Immunol, 2018, 9: 2412. DOI: 10.3389/fimmu.2018.02412.
[25]	CLOUTHIER DL, ZHOU AC, WORTZMAN ME, et al. GITR intrinsically sustains early type 1 and late follicular helper CD4 T cell accumulation to control a chronic viral infection[J]. PLoS Pathog, 2015, 11(1): e1004517. DOI: 10.1371/journal.ppat.1004517.
[26]	KOH CH, KIM IK, SHIN KS, et al. GITR agonism triggers antitumor immune responses through IL21-expressing follicular helper T cells[J]. Cancer Immunol Res, 2020, 8(5): 698-709. DOI: 10.1158/2326-6066.CIR-19-0748.
[27]	KIM IK, KIM BS, KOH CH, et al. Glucocorticoid-induced tumor necrosis factor receptor-related protein co-stimulation facilitates tumor regression by inducing IL-9-producing helper T cells[J]. Nat Med, 2015, 21(9): 1010-1017. DOI: 10.1038/nm.3922.
[28]	KRAUSZ LT, BIANCHINI R, RONCHETTI S, et al. GITR-GITRL system, a novel player in shock and inflammation[J]. Scientific-WorldJournal, 2007, 7: 533-566. DOI: 10.1100/tsw.2007.106.
[29]	NARDELLI B, ZARITSKAYA L, MCAULIFFE W, et al. Osteostat/tumor necrosis factor superfamily 18 inhibits osteoclastogenesis and is selectively expressed by vascular endothelial cells[J]. Endocrinology, 2006, 147(1): 70-78. DOI: 10.1210/en.2005-0518.
[30]	LACAL PM, PETRILLO MG, RUFFINI F, et al. Glucocorticoid-induced tumor necrosis factor receptor family-related ligand triggering upregulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and promotes leukocyte adhesion[J]. J Pharmacol Exp Ther, 2013, 347(1): 164-172. DOI: 10.1124/jpet.113.207605.
[31]	AGOSTINI M, CENCI E, PERICOLINI E, et al. The glucocorticoid-induced tumor necrosis factor receptor-related gene modulates the response to Candida albicans infection[J]. Infect Immun, 2005, 73(11): 7502-7508. DOI: 10.1128/IAI.73.11.7502-7508.2005.
[32]	GROHMANN U, VOLPI C, FALLARINO F, et al. Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy[J]. Nat Med, 2007, 13(5): 579-586. DOI: 10.1038/nm1563.
[33]	LEE HS, SHIN HH, KWON BS, et al. Soluble glucocorticoid-induced tumor necrosis factor receptor (sGITR) increased MMP-9 activity in murine macrophage[J]. J Cell Biochem, 2003, 88(5): 1048-1056. DOI: 10.1002/jcb.10456.
[34]	BAE E, KIM WJ, KANG YM, et al. Glucocorticoid-induced tumour necrosis factor receptor-related protein-mediated macrophage stimulation may induce cellular adhesion and cytokine expression in rheumatoid arthritis[J]. Clin Exp Immunol, 2007, 148(3): 410-418. DOI: 10.1111/j.1365-2249.2007.03363.x.
[35]	BAE EM, KIM WJ, SUK K, et al. Reverse signaling initiated from GITRL induces NF-kappaB activation through ERK in the inflammatory activation of macrophages[J]. Mol Immunol, 2008, 45(2): 523-533. DOI: 10.1016/j.molimm.2007.05.013.
[36]	WEI SD, LI JZ, LIU ZJ, et al. Dexamethasone attenuates lipopolysaccharide-induced liver injury by downregulating glucocorticoid-induced tumor necrosis factor receptor ligand in Kupffer cells[J]. Hepatol Res, 2011, 41(10): 989-999. DOI: 10.1111/j.1872-034X.2011.00852.x.
[37]	WEI S, LI J, LIAN Z, et al. Expression of glucocorticoid-induced tumor necrosis factor receptor ligand in rat graft after liver transplantation[J]. Transplant Proc, 2011, 43(5): 1971-1975. DOI: 10.1016/j.transproceed.2011.03.054.
[38]	WANG W, JI G, CHEN Y, et al. Changes in DNA methylation of glucocorticoid-induced tumor necrosis factor receptor and its ligand in liver transplantation[J]. Transplant Proc, 2017, 49(8): 1824-1833. DOI: 10.1016/j.transproceed.2017.06.023.
[39]	LIAO G, O'KEEFFE MS, WANG G, et al. Glucocorticoid-Induced TNF receptor family-related protein ligand is requisite for optimal functioning of regulatory CD4(+) t cells[J]. Front Immunol, 2014, 5: 35. DOI: 10.3389/fimmu.2014.00035.
[40]	LIAO G, NAYAK S, REGUEIRO JR, et al. GITR engagement preferentially enhances proliferation of functionally competent CD4⁺CD25⁺FoxP3⁺ regulatory T cells[J]. Int Immunol, 2010, 22(4): 259-270. DOI: 10.1093/intimm/dxq001.
[41]	ZHANG HH, MEI MH, FEI R, et al. Regulatory T cells in chronic hepatitis B patients affect the immunopathogenesis of hepatocellular carcinoma by suppressing the anti-tumour immune responses[J]. J Viral Hepat, 2010, 17(Suppl 1): 34-43. DOI: 10.1111/j.1365-2893.2010.01269.x.
[42]	ORMANDY LA, HILLEMANN T, WEDEMEYER H, et al. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma[J]. Cancer Res, 2005, 65(6): 2457-2464. DOI: 10.1158/0008-5472.CAN-04-3232.
[43]	VAN BEEK AA, ZHOU G, DOUKAS M, et al. GITR ligation enhances functionality of tumor-infiltrating T cells in hepatocellular carcinoma[J]. Int J Cancer, 2019, 145(4): 1111-1124. DOI: 10.1002/ijc.32181.
[44]	ZHOU G, SPRENGERS D, MANCHAM S, et al. Reduction of immunosuppressive tumor microenvironment in cholangiocarcinoma by ex vivo targeting immune checkpoint molecules[J]. J Hepatol, 2019, 71(4): 753-762. DOI: 10.1016/j.jhep.2019.05.026.
[45]	CABO M, OFFRINGA R, ZITVOGEL L, et al. Trial Watch: Immunostimulatory monoclonal antibodies for oncological indications[J]. Oncoimmunology, 2017, 6(12): e1371896. DOI: 10.1080/2162402X.2017.1371896.

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Research advances in the role of the glucocorticoid-induced tumor necrosis factor receptor-related protein and its ligand in liver diseases

DOI: 10.3969/j.issn.1001-5256.2021.07.051

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