Skip to main content
SpringerLink
Log in

GITR: A Modulator of Immune Response and Inflammation

  • Chapter
Book cover Therapeutic Targets of the TNF Superfamily

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 647))

Abstract

Glucocorticoid-Induced TNFR-Related (GITR) protein belongs to Tumor Necrosis Factor Receptor Superfamily (TNFRSF) and stimulates both the acquired and innate immunity. It is expressed in several cells and tissues, including T and Natural Killer (NK) cells and is activated by its ligand, GITRL, mainly expressed on Antigen Presenting Cells (APCs) and endothelial cells. GITR/GITRL system participates in the development of autoimmune/inflammatory responses and graft vs. host disease and potentiates response to infection and tumors. These effects are due to several concurrent mechanisms including: co-activation of effector T-cells, inhibition of regulatory T (Treg) cells, NK-cell co-activation, activation of macrophages, modulation of DC function and regulation of the extravasation process. In this chapter we describe: 1) the main structural features of GITR and GITRL, 2) the transduction pathways activated by GITR triggering, 3) the effects derived from GITR/GITRL system interaction, considering the interplay between the different cells of the immune system. Moreover, the potential use of GITR/GITRL modulators in disease treatment is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Sakaguchi S, Sakaguchi N, Asano M et al. Immunologic self-tolerance maintained by activated T-cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995; 155(3):1151–1164.

    PubMed  CAS  Google Scholar 

  2. Beissert S, Schwarz A, Schwarz T. Regulatory T-cells. J Invest Dermatol 2006; 126(1):15–24.

    Article  PubMed  CAS  Google Scholar 

  3. Watts TH. TNF/TNFR family members in costimulation of T-cell responses. Annu Rev Immunol 2005; 23:23–68.

    Article  PubMed  CAS  Google Scholar 

  4. 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. Proc Natl Acad Sci USA 1997; 94(12):6216–6221.

    Article  PubMed  CAS  Google Scholar 

  5. Bossen C, Ingold K, Tardivel A et al. Interactions of Tumor Necrosis Factor (TNF) and TNF Receptor Family Members in the Mouse and Human. J Biol Chem 2006; 281(20):13964–14971.

    Article  PubMed  CAS  Google Scholar 

  6. Kwon B, Yu KY, Ni J et al. Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand. J Biol Chem 1999; 274(10):6056–6061.

    Article  PubMed  CAS  Google Scholar 

  7. 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. Curr Biol 1999; 9(4):215–218.

    Article  PubMed  CAS  Google Scholar 

  8. Kim JD, Choi BK, Bae JS et al. Cloning and characterization of GITR ligand. Genes Immun 2003; 4(8):564–569.

    Article  PubMed  CAS  Google Scholar 

  9. Tone M, Tone Y, Adams E et al. Mouse glucocorticoid-induced tumor necrosis factor receptor ligand is costimulatory for T-cells. Proc Natl Acad Sci USA 2003; 100(25):15059–15064.

    Article  PubMed  CAS  Google Scholar 

  10. Yu KY, Kim HS, Song SY. USA. Identification of a ligand for glucocorticoid-induced tumor necrosis factor receptor constitutively expressed in dendritic cells. Biochem Biophys Res Commun 2003; 310(2):433–438.

    Article  PubMed  CAS  Google Scholar 

  11. Ronchetti S, Zollo O, Bruscoli S et al. GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T-lymphocyte subpopulations. Eur J Immunol 2004; 34(3):613–622.

    Article  PubMed  CAS  Google Scholar 

  12. Nocentini G, Bartoli A, Ronchetti S et al. Gene structure and chromosomal assignment of mouse GITR, a member of the tumor necrosis factor/nerve growth factor receptor family. DNA Cell Biol 2000; 19(4):205–217.

    Article  PubMed  CAS  Google Scholar 

  13. Nocentini G, Ronchetti S, Bartoli A et al. Identification of three novel mRNA splice variants of GITR. Cell Death Differ 2000; 7(4):408–410.

    Article  PubMed  CAS  Google Scholar 

  14. Spinicelli S, Nocentini G, Ronchetti S et al. GITR interacts with the pro-apoptotic protein Siva and induces apoptosis. Cell Death Differ 2002; 9(12):1382–1384.

    Article  PubMed  CAS  Google Scholar 

  15. Esparza EM, Arch RH. Glucocorticoid-induced TNF receptor functions as a costimulatory receptor that promotes survival in early phases of T-cell activation. J Immunol 2005; 174(12):7869–7874.

    PubMed  CAS  Google Scholar 

  16. Esparza EM, Arch RH. Glucocorticoid-induced TNF receptor, a costimulatory receptor on naive and activated T-cells, uses TNF receptor-associated factor 2 in a novel fashion as an inhibitor of NF-kappa B activation. J Immunol 2005; 174(12):7875–7882.

    PubMed  CAS  Google Scholar 

  17. Prasad KV, Ao Z, Yoon Y et al. CD27, a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, a proapoptotic protein. Proc Natl Acad Sci USA 1997; 94(12):6346–6351.

    Article  PubMed  CAS  Google Scholar 

  18. Py B, Slomianny C, Auberger P et al. Siva-1 and an alternative splice form lacking the death domain, Siva-2, similarly induce apoptosis in T-lymphocytes via a caspase-dependent mitochondrial pathway. J Immunol 2004; 172(7):4008–4017.

    PubMed  CAS  Google Scholar 

  19. Lin WJ, Gary JD, Yang MC et al. The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase. J Biol Chem 1996; 271(25):15034–15044.

    Article  PubMed  CAS  Google Scholar 

  20. An W, Kim J, Roeder RG. Ordered cooperative functions of PRMT1, p.300 and CARM1 in transcriptional activation by p.53 Cell 2004; 117(6):735–748.

    Article  PubMed  CAS  Google Scholar 

  21. Ganesh L, Yoshimoto T, Moorthy NC et al. Protein methyltransferase 2 inhibits NF-kappaB function and promotes apoptosis. Mol Cell Biol 2006; 26(10):3864–3874.

    Article  PubMed  CAS  Google Scholar 

  22. McHugh RS, Whitters MJ, Piccirillo CA et al. CD4(+)CD25(+) immunoregulatory T-cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 2002; 16(2):311–323.

    Article  PubMed  CAS  Google Scholar 

  23. 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 Immunol 2004; 172(8):4686–4690.

    PubMed  CAS  Google Scholar 

  24. Kanamaru F, Youngnak P, Hashiguchi M et al. Costimulation via glucocorticoid-induced TNF receptor in both conventional and CD25+ regulatory CD4+ T-cells. J Immunol 2004; 172(12):7306–7314.

    PubMed  CAS  Google Scholar 

  25. Stephens GL, McHugh RS, Whitters MJ et al. Engagement of glucocorticoid-induced TNFR family-related receptor on effector T-cells by its ligand mediates resistance to suppression by CD4+CD25+ T-cells. J Immunol 2004; 173(8):5008–5020.

    PubMed  CAS  Google Scholar 

  26. Zelenika D, Adams E, Humm S et al. Regulatory T-cells overexpress a subset of Th2 gene transcripts. J Immunol 2002; 168(3):1069–1079.

    PubMed  CAS  Google Scholar 

  27. Shimizu J, Yamazaki S, Takahashi T et al. Stimulation of CD25(+)CD4(+) regulatory T-cells through GITR breaks immunological self-tolerance. Nat Immunol 2002; 3(2):135–142.

    Article  PubMed  CAS  Google Scholar 

  28. Uraushihara K, Kanai T, Ko K et al. Regulation of murine inflammatory bowel disease by CD25+ and CD25-CD4+ glucocorticoid-induced TNF receptor family-related gene+regulatory T-cells. J Immunol 2003; 171(2):708–716.

    PubMed  CAS  Google Scholar 

  29. Scotto L, Naiyer AJ, Galluzzo S et al. Overlap between molecular markers expressed by naturally occurring CD4+CD25+ regulatory T-cells and antigen specific CD4+CD25+ and CD8+CD28-T suppressor cells. Hum Immunol 2004; 65(11):1297–1306.

    Article  PubMed  CAS  Google Scholar 

  30. Cosmi L, Liotta F, Lazzeri E et al. Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood 2003; 102(12):4107–4114.

    Article  PubMed  CAS  Google Scholar 

  31. Kim HJ, Kim HY, Kim BK et al. Engagement of glucocorticoid-induced TNF receptor costimulates NKT-cell activation in vitro and in vivo. J Immunol 2006; 176(6):3507–3515.

    PubMed  CAS  Google Scholar 

  32. Hanabuchi S, Watanabe N, Wang YH et al. Human plasmacytoid predendritic cells activate NK-cells through glucocorticoid-induced tumor necrosis factor receptor-ligand (GITRL). Blood 2006; 107(9):3617–3623.

    Article  PubMed  CAS  Google Scholar 

  33. Cuzzocrea S, Nocentini G, Di Paola R et al. Proinflammatory role of glucocorticoid-induced TNF receptor-related gene in acute lung inflammation. J Immunol 2006; 177(1):631–641.

    PubMed  CAS  Google Scholar 

  34. Santucci L, Agostini M, Bruscoli S et al. GITR modulates innate and adaptive mucosal immunity during the development of experimental colitis in mice. Gut 2006.

    Google Scholar 

  35. Nakae S, Suto H, Iikura M et al. Mast cells enhance T-cell activation: importance of mast cell costimulatory molecules and secreted TNF. J Immunol 2006; 176(4):2238–2248.

    PubMed  CAS  Google Scholar 

  36. Wang J, Devgan V, Corrado M et al. Glucocorticoid-induced tumor necrosis factor receptor is a p21Cip1/WAF1 transcriptional target conferring resistance of keratinocytes to UV light-induced apoptosis. J Biol Chem 2005; 280(45):37725–37731.

    Article  PubMed  CAS  Google Scholar 

  37. Shin HH, Kim SJ, Kang SY et al. Soluble glucocorticoid-induced tumor necrosis factor receptor stimulates osteoclastogenesis by down-regulation of osteoprotegerin in bone marrow stromal cells. Bone 2006.

    Google Scholar 

  38. Shin HH, Kim SJ, Lee DS et al. Soluble glucocorticoid-induced tumor necrosis factor receptor (sGITR) stimulates osteoclast differentiation in response to receptor activator of NF-kappaB ligand (RANKL) in osteoclast cells. Bone 2005; 36(5):832–839.

    Article  PubMed  CAS  Google Scholar 

  39. Kim BJ, Li Z, Fariss RN et al. Constitutive and cytokine-induced GITR ligand expression on human retinal pigment epithelium and photoreceptors. Invest Ophthalmol Vis Sci 2004; 45(9):3170–3176.

    Article  PubMed  Google Scholar 

  40. Agostini M, Cenci E, Pericolini E et al. The glucocorticoid-induced tumor necrosis factor receptor-related gene modulates the response to Candida albicans infection. Infect Immun 2005; 73(11):7502–7508.

    Article  PubMed  CAS  Google Scholar 

  41. Shin HH, Kim SJ, Lee HS et al. The soluble glucocorticoid-induced tumor necrosis factor receptor causes cell cycle arrest and apoptosis in murine macrophages. Biochem Biophys Res Commun 2004; 316(1):24–32.

    Article  PubMed  CAS  Google Scholar 

  42. Shin HH, Kim SG, Lee MH et al. Soluble glucocorticoid-induced TNF receptor (sGITR) induces inflammation in mice. Exp Mol Med 2003; 35(5):358–364.

    PubMed  CAS  Google Scholar 

  43. Cardona ID, Goleva E, Ou LS et al. Staphylococcal enterotoxin B inhibits regulatory T-cells by inducing glucocorticoid-induced TNF receptor-related protein ligand on monocytes. J Allergy Clin Immunol 2006; 117(3):688–695.

    Article  PubMed  CAS  Google Scholar 

  44. Suvas S, Kim B, Sarangi PP et al. In vivo kinetics of GITR and GITR ligand expression and their functional significance in regulating viral immunopathology. J Virol 2005; 79(18):11935–11942.

    Article  PubMed  CAS  Google Scholar 

  45. Shevach EM, Stephens GL. The GITR-GITRL interaction: costimulation or contrasuppression of regulatory activity? Nat Rev Immunol 2006; 6(8):613–618.

    Article  PubMed  CAS  Google Scholar 

  46. Nardelli B, Zaritskaya L, McAuliffe W et al. Osteostat/tumor necrosis factor superfamily 18 inhibits osteoclastogenesis and is selectively expressed by vascular endothelial cells. Endocrinology 2006; 147(1):70–78.

    Article  PubMed  CAS  Google Scholar 

  47. Cuzzocrea S, Ayroldi E, Di Paola R et al. Role of glucocorticoid-induced TNF receptor family gene (GITR) in collagen-induced arthritis. FASEB J 2005; 19(10):1253–1265.

    Article  PubMed  CAS  Google Scholar 

  48. Patel M, Xu D, Kewin P et al. Glucocorticoid-induced TNFR family-related protein (GITR) activation exacerbates murine asthama and collagen-induced arthritis. Eur J Immunol 2005; 35(12):3581–3590.

    Article  PubMed  CAS  Google Scholar 

  49. Cuzzocrea S, Ronchetti S, Genovese T et al. Genetic and pharmacological inhibition of GITR-GITRL interaction reduces chronic lung injury induced by bleomycin instillation. FASEB J 2007; 21(1):117–129.

    Article  PubMed  CAS  Google Scholar 

  50. Lee SK, Choi BK, Kim YH et al. Glucocorticoid-induced tumour necrosis factor receptor family-related receptor signalling exacerbates hapten-induced colitis by CD4+ T-cells. Immunology 2006; 119(4):479–487.

    Article  PubMed  CAS  Google Scholar 

  51. Muriglan SJ, Ramirez-Montagut T, Alpdogan O et al. GITR activation induces an opposite effect on alloreactive CD4(+) and CD8(+) T-cells in graft-versus-host disease. J Exp Med 2004; 200(2):149–157.

    Article  PubMed  CAS  Google Scholar 

  52. Kim J, Choi WS, Kim HJ et al. Prevention of chronic graft-versus-host disease by stimulation with glucocorticoid-induced TNF receptor. Exp Mol Med 2006; 38(1):94–99.

    PubMed  CAS  Google Scholar 

  53. Kim J, Choi WS, Kang H et al. Conversion of alloantigen-specific CD8+ T-cell anergy to CD8+ T-cell priming through in vivo ligation of glucocorticoid-induced TNF receptor. J Immunol 2006; 176(9):5223–5231.

    PubMed  CAS  Google Scholar 

  54. Suri A, Shimizu J, Katz JD et al. Regulation of autoimmune diabetes by non-islet-specific T-cells—a role for the glucocorticoid-induced TNF receptor. Eur J Immunol 2004; 34(2):447–454.

    Article  PubMed  CAS  Google Scholar 

  55. Morris GP, Kong YC. Interference with CD4+CD25+ T-cell-mediated tolerance to experimental autoimmune thyroiditis by glucocorticoid-induced tumor necrosis factor receptor monoclonal antibody. J Autoimmun 2006; 26(1):24–31.

    Article  PubMed  CAS  Google Scholar 

  56. He H, Messer RJ, Sakaguchi S et al. Reduction of retrovirus-induced immunosuppression by in vivo modulation of T-cells during acute infection. J Virol 2004; 78(21):11641–11647.

    Article  PubMed  CAS  Google Scholar 

  57. Dittmer U, He H, Messer RJ et al. Functional impairment of CD8(+) T-cells by regulatory T-cells during persistent retroviral infection. Immunity 2004; 20(3):293–303.

    Article  PubMed  CAS  Google Scholar 

  58. Stone GW, Barzee S, Snarsky V et al. Multimeric soluble CD40 ligand and GITR ligand as adjuvants for human immunodeficiency virus DNA vaccines. J Virol 2006; 80(4):1762–1772.

    Article  PubMed  CAS  Google Scholar 

  59. Taylor MD, LeGoff L, Harris A et al. Removal of regulatory T-cell activity reverses hyporesponsiveness and leads to filarial parasite clearance in vivo. J Immunol 2005; 174(8):4924–4933.

    PubMed  CAS  Google Scholar 

  60. Turk MJ, Guevara-Patino JA, Rizzuto GA et al. Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T-cells. J Exp Med 2004; 200(6):771–782.

    Article  PubMed  CAS  Google Scholar 

  61. Calmels B, Paul S, Futin N et al. Bypassing tumor-associated immune suppression with recombinant adenovirus constructs expressing membrane bound or secreted GITR-L. Cancer Gene Ther 2005; 12(2):198–205.

    Article  PubMed  CAS  Google Scholar 

  62. 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 Exp Med 2005; 202(7):885–891.

    Article  PubMed  CAS  Google Scholar 

  63. Cohen AD, Diab A, Perales MA et al. Agonist anti-GITR antibody enhances vaccine-induced CD8(+) T-cell responses and tumor immunity. Cancer Res 2006; 66(9):4904–4912.

    Article  PubMed  CAS  Google Scholar 

  64. Cuzzocrea S, Nocentini G, Di Paola R et al. Glucocorticoid-induced TNF receptor family gene (GITR) knockout mice exhibit a resistance to splanchnic artery occlusion (SAO) shock. J Leukoc Biol 2004; 76(5):933–940.

    Article  PubMed  CAS  Google Scholar 

  65. Nocentini G, Riccardi C. GITR: a multifaceted regulator of immunity belonging to the tumor necrosis factor receptor superfamily. Eur J Immunol 2005; 35(4):1016–1022.

    Article  PubMed  CAS  Google Scholar 

  66. Esparza EM, Arch RH. Signaling triggered by glucocorticoid-induced tumor necrosis factor receptor family-related gene: regulation at the interface between regulatory T-cells and immune effector cells. Front Biosci 2006; 11:1448–1465.

    Article  PubMed  CAS  Google Scholar 

  67. Mahesh SP, Li Z, Liu B et al. Expression of GITR ligand abrogates immunosuppressive function of ocular tissue and differentially modulates inflammatory cytokines and chemokines. Eur J Immunol 2006; 36(8):2128–2138.

    Article  PubMed  CAS  Google Scholar 

  68. 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. Cell Immunol 2005; 235(1):56–64.

    Article  PubMed  CAS  Google Scholar 

  69. Ji HB, Liao G, Faubion WA et al. Cutting edge: the natural ligand for glucocorticoid-induced TNF receptor-related protein abrogates regulatory T-cell suppression. J Immunol 2004; 172(10):5823–5827.

    PubMed  CAS  Google Scholar 

  70. Shimizu J, Moriizumi E. CD4+CD25−T-cells in aged mice are hyporesponsive and exhibit suppressive activity. J Immunol 2003; 170(4):1675–1682.

    PubMed  CAS  Google Scholar 

  71. Tsaknaridis L, Spencer L, Culbertson N et al. Functional assay for human CD4+CD25+ Treg cells reveals an age-dependent loss of suppressive activity. J Neurosci Res 2003; 74(2):296–308.

    Article  PubMed  CAS  Google Scholar 

  72. Gondek DC, Lu LF, Quezada SA et al. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J Immunol 2005; 174(4):1783–1786.

    PubMed  CAS  Google Scholar 

  73. Valzasina B, Guiducci C, Dislich H et al. Triggering of OX40 (CD134) on CD4(+)CD25+ T-cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR. Blood 2005; 105(7):2845–2851.

    Article  PubMed  CAS  Google Scholar 

  74. Ramirez-Montagut T, Chow A, Hirschhorn-Cymerman D et al. Glucocorticoid-Induced TNF Receptor Family Related Gene Activation Overcomes Tolerance/Ignorance to Melanoma Differentiation Antigens and Enhances Antitumor Immunity. J Immunol 2006; 176(11):6434–6442.

    PubMed  CAS  Google Scholar 

  75. Shin HH, Kwon BS, Choi HS. Recombinant glucocorticoid induced tumour necrosis factor receptor (rGITR) induced COX-2 activity in murine macrophage Raw 264.7 cells. Cytokine 2002; 19(4):187–192.

    Article  PubMed  CAS  Google Scholar 

  76. Shin HH, Lee HW, Choi HS. Induction of nitric oxide synthase (NOS) by soluble glucocorticoid induced tumor necrosis factor receptor (sGITR) is modulated by IFN-gamma in murine macrophage. Exp Mol Med 2003; 35(3):175–180.

    PubMed  CAS  Google Scholar 

  77. Kim SJ, Shin HH, Park SY et al. Induction of MMP-13 expression by soluble human glucocorticoid-induced tumor necrosis factor receptor in fibroblast-like synovial cells. Osteoarthritis Cartilage 2006; 14(2):146–153.

    Article  PubMed  CAS  Google Scholar 

  78. Lee HS, Shin HH, Kwon BS et al. Soluble glucocorticoid-induced tumor necrosis factor receptor (sGITR) increased MMP-9 activity in murine macrophage. J Cell Biochem 2003; 88(5):1048–1056.

    Article  PubMed  CAS  Google Scholar 

  79. Kim WJ, Bae EM, Kang YJ et al. Glucocorticoid-induced tumour necrosis factor receptor family related protein (GITR) mediates inflammatory activation of macrophages that can destabilize atherosclerotic plaques. Immunology 2006; 119(3):421–429.

    Article  PubMed  CAS  Google Scholar 

  80. Shin HH, Lee MH, Kim SG et al. Recombinant glucocorticoid induced tumor necrosis factor receptor (rGITR) induces NOS in murine macrophage. FEBS Lett 2002; 514(2–3):275–280.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dipartimento di Medicina Clinica e Sperimentale, Sezione di Farmacologia, Università di Perugia, Via del Giochetto, 06100, Perugia, Italy

    Giuseppe Nocentini & Carlo Riccardi

  2. Polo Scientifico e Didattico di Terni, Perugia, Italy

    Carlo Riccardi

Authors
  1. Giuseppe Nocentini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlo Riccardi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Preclinical Therapeutics, Seattle Genetics, Inc., Bothell, Washington, USA

    Iqbal S. Grewal PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Nocentini, G., Riccardi, C. (2009). GITR: A Modulator of Immune Response and Inflammation. In: Grewal, I.S. (eds) Therapeutic Targets of the TNF Superfamily. Advances in Experimental Medicine and Biology, vol 647. Springer, New York, NY. https://doi.org/10.1007/978-0-387-89520-8_11

Download citation

Publish with us

Policies and ethics

Search

Navigation