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Immunologic Research

, Volume 36, Issue 1–3, pp 147–155 | Cite as

Immune regulation by the TIM gene family

  • Anjali J. de Souza
  • Lawrence P. Kane
Article

Abstract

Recent studies have demonstrated that proteins of the T cell immunologobulin and mucin domain (TIM) family are important regulators of immune function. Here we discuss the functional effects of TIM proteins on immune responses, how the effects of TIM proteins may be modulated by interactions with ligands and the limited information available on intracellular signals downstream of TIM proteins.

Key Words

T cells Activation Asthma Autoimmunity Co-stimulation Mucins 

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References

  1. 1.
    Ober C, Hoffjan S: Asthma genetics 2006: the long and winding road to gene discovery. Genes Immun 2006; 7:95–100.PubMedCrossRefGoogle Scholar
  2. 2.
    Wills-Karp M, Ewart SL: Time to draw breath: asthmasusceptibility genes are identified. Nat Rev Genet 2004;5:376–387.PubMedCrossRefGoogle Scholar
  3. 3.
    McIntire JJ, Umetsu SE, Akbari O, et al: Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family. Nat Immunol 2001;2:1109–1116.PubMedCrossRefGoogle Scholar
  4. 4.
    Meyers JH, Sabatos CA, Chakravarti S, Kuchroo VK: The TIM gene family regulates autoimmune and allergic diseases. Trends Mol Med 2005;11:362–369.PubMedCrossRefGoogle Scholar
  5. 5.
    Monney L, Sabatos CA, Gaglia JL, et al: Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature 2002;415:536–541.PubMedCrossRefGoogle Scholar
  6. 6.
    Kaplan G, Totsuka A, Thompson P, Akatsuka T, Moritsugu Y, Feinstone SM. Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus. EMBO J 1996; 15:4282–4296.PubMedGoogle Scholar
  7. 7.
    Feigelstock D, Thompson P, Mattoo P, Zhang Y, Kaplan GG: The human homolog of HAV cr-1 codes for a hepatitis A virus cellular receptor. J Virol 1998;72: 6621–6628.PubMedGoogle Scholar
  8. 8.
    Ichimura T, Bonventre JV, Bailly V, et al: Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem 1998;273:4135–4142.PubMedCrossRefGoogle Scholar
  9. 9.
    Umetsu SE, Lee WL, McIntire JJ, et al: TIM-1 induces T cell activation and inhibits the development of peripheral tolerance. Nat Immunol 2005:447–454.Google Scholar
  10. 10.
    Chakravarti S, Sabatos CA, Xiao S, et al: Tim-2 regulates T helper type 2 responses and autoimmunity. J Exp Med 2005;202:437–444.PubMedCrossRefGoogle Scholar
  11. 11.
    Chen TT, Li L, Chung DH, et al: TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. J Exp Med 2005;202:955–965.PubMedCrossRefGoogle Scholar
  12. 12.
    Sanchez-Fueyo A, Tian J, Picarella D, et al: Tim-3 inhibits T helper type 1-mediated auto- and alloimmune resplonses and promotes immunological tolerance. Nat Immunol 2003:4:1093–1101.PubMedCrossRefGoogle Scholar
  13. 13.
    Zhu C, Anderson AC, Schubart A, et al: The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol 2005;6:1245–1252.PubMedCrossRefGoogle Scholar
  14. 14.
    Sabatos CA, Chakravarti S, Cha E, et al: Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance. Nat Immunol 2003;4:1102–1110.PubMedCrossRefGoogle Scholar
  15. 15.
    Shakhov AN, Rybtsov S, Tumanov AV, et al: SMUCK-LER/TIM4 is a distinct member of TIM family expressed by stromal cells of secondary lymphoid tissues and associated with lymphotox in signaling. Eur J Immunol 2004;34:494–503.PubMedCrossRefGoogle Scholar
  16. 16.
    Meyers JH, Chakravarti S, Schlesinger D, et al: TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T cell proliferation. Nat Immunol 2005;6:455–464.PubMedCrossRefGoogle Scholar
  17. 17.
    Mesri M, Smithson G, Ghatpande A, et al: Inhibition of in vitro and in vivo T cell responses by, recombinant human Tim-1 extracellular domain proteins. Int Immunol 2006;18:473–484.PubMedCrossRefGoogle Scholar
  18. 18.
    de Souza AJ, Oriss TB, O'Malley K, Ray A, Kane LP: TIM-1 is expressed on in vivo-activated T cells and provides a co-stimulatory signal for T cell activation. Proc Natl Acad Sci USA 2005:102:17113–17118.PubMedCrossRefGoogle Scholar
  19. 19.
    Theil EC; Ferritin: structure, gene regulation, and cellular function in animals, plants, and microorganisms. Annu Rev Biochem 1987;56:289–315.PubMedCrossRefGoogle Scholar
  20. 20.
    Kumanogoh A, Marukawa S, Suzuki K, et al: Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2. Nature 2002;419:629–633.PubMedCrossRefGoogle Scholar
  21. 21.
    Matsushita N, Nishi N, Seki M, et al: Requirement of divalent galactoside-binding activity of ecalectin/glectin-9 for eosinophil chemoattraction. J Biol Chem 2000;275:8355–8360.PubMedCrossRefGoogle Scholar
  22. 22.
    Berg EL, McEvoy LM, Berlin C, Bargatze RF, Butcher EC: L-selectin-mediated lymphocyte rolling on MAdCAM-1. Nature 1993;366:695–698.PubMedCrossRefGoogle Scholar
  23. 23.
    Kane LP, Lin J, Weiss A. It's all Rel-ative: NF-kappaB and CD28 costimulation of T-cell activation. Trends Immunol 2002;23:413–420.PubMedCrossRefGoogle Scholar
  24. 24.
    Watts TH: TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol 2005;23:23–68.PubMedCrossRefGoogle Scholar
  25. 25.
    Croft M: Costimulation of T cells by OX40, 4-1BB, and CD27. Cytokine Growth Factor Rev 2003;14: 265–273.PubMedCrossRefGoogle Scholar
  26. 26.
    Lenschow DJ, Valunas TL, Bluestone JA: CD28/B7 system of T cell costimulation. Annu Rev Immunol 1996;14:233–258.PubMedCrossRefGoogle Scholar
  27. 27.
    Encinas JA, Janssen EM, Weiner DB, et al: Anti-T-cell Ig and mucin domain-containg protein 1 antibody decreases TH2 airway inflammation in a mouse model of asthma. J Allergy Clin Immunol 2005;116: 1343–1349.PubMedCrossRefGoogle Scholar
  28. 28.
    Kumanogoh A Shikina T, Suzuki K, et al: Nonredundant roles of Sema4A in the immune system: defective T cell priming and Th1/Th2 regulation in Sema4A-deficient mice. Immunity 2005;22:305–316.PubMedCrossRefGoogle Scholar
  29. 29.
    Lipschitz DA, Cook JD, Finch CA: A clinical evaluation of serum ferritin as an index of iron stores. N Engl J Med 1974;290:1213–1216.PubMedCrossRefGoogle Scholar
  30. 30.
    Broxmeyer HE, Williams DE, Geissler K, et al: Suppressive effects in vivo of purified recombinant human H-subunit (acidic) ferritin on murine myelopoiesis. Blood 1989;73:74–79.PubMedGoogle Scholar
  31. 31.
    de Sousa M, Smithyman A, Tan C: Suggested models of ecotaxopathy in lymphoreticular malignancy. A role for iron-binding proteins in the control of lymphoid cell migration. Am J Pathol 1978;90:497–520.PubMedGoogle Scholar
  32. 32.
    Matzner Y, Hershko C, Polliack A, Konijn AM, Izak G: Suppressive effect of ferritin on in vitro lymphocyte function. Br J Haematol 1979;42:345–353.PubMedGoogle Scholar
  33. 33.
    Gray CP, Franco AV, Arosio P, Hersey P: Immunosuppressive effects of melanoma-derived heavy-chain ferritin are dependent on stimulation of IL-10 production. Int J Cancer 2001;92:843–850.PubMedCrossRefGoogle Scholar
  34. 34.
    Gray CP, Arosio P, Hersey P: Heavy chain ferritin activates regulatory T cells by induction of changes in dendritic cells. Blood 2002;99:3326–3334.PubMedCrossRefGoogle Scholar
  35. 35.
    Kashio Y, Nakamura K, Abedin MJ, et al: Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway. J Immunol 2003;170:3631–3636.PubMedGoogle Scholar
  36. 36.
    Wada J, Ota K, Kumar A, Wallner EI, Kanwar YS: Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin. J Clin Invest 1997;99:2452–2461.PubMedCrossRefGoogle Scholar
  37. 37.
    Imaizumi T, Kumagai M, Sasaki N, et al: Interferon-gamma stimulates the expression of galectin-9 in cultured human endothelial cells. J Leukoc Biol 2002;72: 486–491.PubMedGoogle Scholar
  38. 38.
    Yoshida H, Imaizumi T, Kumagai M, et al: Interleukin-Ibeta stimulates galectin-9 expression in human astrocytes. Neuroreport 2001;12:3755–3758.PubMedCrossRefGoogle Scholar
  39. 39.
    Knickelbein JE, de Souza AJ, Tosti R, Narayan P, Kane LP: Cutting edge: inhibiton of T cell activation by TIM-2. J Immunol 2006;177:4966–4970.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Anjali J. de Souza
    • 1
  • Lawrence P. Kane
    • 1
  1. 1.Department of ImmunologyUniversity of Pittsburgh School of MedicinePittsburgh

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