Immune Semaphorins: Novel Features of Neural Guidance Molecules

  • Masayuki Mizui
  • Atsushi Kumanogoh
  • Hitoshi Kikutani



The immune and nervous system have various common features in the functional characteristics. Both have an intricate network of synaptic connections and an exquisite communication system that enables intercellular signal transduction. They also share a number of messenger molecules such as cytokines and chemical mediators.


Semaphorins, well-defined axonal guidance molecules in the nervous system, also play critical roles in immune regulation. Various types of semaphorins, including secreted, transmembrane, truncated, and glycosylphosphatidylinositol-anchored forms, function during immune responses. However, some semaphorins utilize receptors in the immune system that are distinct from receptors in the nervous system.


This review presents a current overview of ‘immune semaphorins’ and their receptors, providing insight into the pleiotropic activity of this protein family.


Semaphorins semaphorin receptors immune regulation autoimmune disease allergy 



We thank K. Kubota for secretarial assistance. This study was supported by the Core Research for Evolutional Science and Technology program of the Japanese Science and Technology Agency and Grant-in-Aid for Scientific Research (S)-20229007 of the Japan Society for the Promotion of Science.


  1. 1.
    Steinman L. Elaborate interactions between the immune and nervous systems. Nat Immunol. 2004;5:575–81. doi: 10.1038/ni1078.PubMedCrossRefGoogle Scholar
  2. 2.
    Kolodkin AL, Matthes DJ, Goodman CS. The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell 1993;75:1389–99. doi: 10.1016/0092-8674(93)90625-Z.PubMedCrossRefGoogle Scholar
  3. 3.
    Semaphorin Nomenclature Committee. Unified nomenclature for the semaphorins/collapsins. Cell 1999;97:551–2. doi: 10.1016/S0092-8674(00)80766-7.CrossRefGoogle Scholar
  4. 4.
    Zhou Y, Gunput RA, Pasterkamp RJ. Semaphorin signaling: progress made and promises ahead. Trends Biochem Sci. 2008;33:161–70. doi: 10.1016/j.tibs.2008.01.006.PubMedCrossRefGoogle Scholar
  5. 5.
    Tamagnone L, Artigiani S, Chen H, He Z, Ming GI, Song H, et al. Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 1999;99:71–80. doi: 10.1016/S0092-8674(00)80063-X.PubMedCrossRefGoogle Scholar
  6. 6.
    Winberg ML, Noordermeer JN, Tamagnone L, Comoglio PM, Spriggs MK, Tessier-Lavigne M, et al. Plexin A is a neuronal semaphorin receptor that controls axon guidance. Cell 1998;95:903–16. doi: 10.1016/S0092-8674(00)81715-8.PubMedCrossRefGoogle Scholar
  7. 7.
    Kruger RP, Aurandt J, Guan KL. Semaphorins command cells to move. Nat Rev Mol Cell Biol. 2005;6:789–800. doi: 10.1038/nrm1740.PubMedCrossRefGoogle Scholar
  8. 8.
    Takahashi T, Fournier A, Nakamura F, Wang LH, Murakami Y, Kalb RG, et al. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell 1999;99:59–69. doi: 10.1016/S0092-8674(00)80062-8.PubMedCrossRefGoogle Scholar
  9. 9.
    Toyofuku T, Kikutani H. Semaphorin signaling during cardiac development. Adv Exp Med Biol. 2007;600:109–17. doi: 10.1007/978-0-387-70956-7_9.PubMedCrossRefGoogle Scholar
  10. 10.
    Geretti E, Shimizu A, Klagsbrun M. Neuropilin structure governs VEGF and semaphorin binding and regulates angiogenesis. Angiogenesis 2008;11:31–9. doi: 10.1007/s10456-008-9097-1.PubMedCrossRefGoogle Scholar
  11. 11.
    Toyofuku T, Yabuki M, Kamei J, Kamei M, Makino N, Kumanogoh A, et al. Semaphorin-4A, an activator for T-cell-mediated immunity, suppresses angiogenesis via Plexin-D1. EMBO J. 2007;26:1373–84. doi: 10.1038/sj.emboj.7601589.PubMedCrossRefGoogle Scholar
  12. 12.
    Casazza A, Fazzari P, Tamagnone L. Semaphorin signals in cell adhesion and cell migration: functional role and molecular mechanisms. Adv Exp Med Biol. 2007;600:90–108. doi: 10.1007/978-0-387-70956-7_8.PubMedCrossRefGoogle Scholar
  13. 13.
    Giordano S, Corso S, Conrotto P, Artigiani S, Gilestro G, Barberis D, et al. The semaphorin 4D receptor controls invasive growth by coupling with Met. Nat Cell Biol. 2002;4:720–4. doi: 10.1038/ncb843.PubMedCrossRefGoogle Scholar
  14. 14.
    Bielenberg DR, Klagsbrun M. Targeting endothelial and tumor cells with semaphorins. Cancer Metastasis Rev. 2007;26:421–31. doi: 10.1007/s10555-007-9097-4.PubMedCrossRefGoogle Scholar
  15. 15.
    Suzuki K, Kumanogoh A, Kikutani H. Semaphorins and their receptors in immune cell interactions. Nat Immunol. 2008;9:17–23. doi: 10.1038/ni1553.PubMedCrossRefGoogle Scholar
  16. 16.
    Kikutani H, Suzuki K, Kumanogoh A. Immune semaphorins: increasing members and their diverse roles. Adv Immunol. 2007;93:121–43. doi: 10.1016/S0065-2776(06)93003-X.PubMedCrossRefGoogle Scholar
  17. 17.
    Kikutani H, Kumanogoh A. Semaphorins in interactions between T cells and antigen-presenting cells. Nat Rev Immunol. 2003;3:159–67. doi: 10.1038/nri1003.PubMedCrossRefGoogle Scholar
  18. 18.
    Toyofuku T, Zhang H, Kumanogoh A, Takegahara N, Suto F, Kamei J, et al. Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2. Genes Dev. 2004;18:435–47. doi: 10.1101/gad.1167304.PubMedCrossRefGoogle Scholar
  19. 19.
    Kumanogoh A, Watanabe C, Lee I, Wang X, Shi W, Araki H, et al. Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling. Immunity 2000;13:621–31. doi: 10.1016/S1074-7613(00)00062-5.PubMedCrossRefGoogle Scholar
  20. 20.
    Kumanogoh A, Marukawa S, Suzuki K, Takegahara N, Watanabe C, Ch, ng E, et al. Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2. Nature 2002;419:629–33. doi: 10.1038/nature01037.PubMedCrossRefGoogle Scholar
  21. 21.
    Hall KT, Boumsell L, Schultze JL, Boussiotis VA, Dorfman DM, Cardoso AA, et al. Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation. Proc Natl Acad Sci USA. 1996;93:11780–5. doi: 10.1073/pnas.93.21.11780.PubMedCrossRefGoogle Scholar
  22. 22.
    Furuyama T, Inagaki S, Kosugi A, Noda S, Saitoh S, Ogata M, et al. Identification of a novel transmembrane semaphorin expressed on lymphocytes. J Biol Chem. 1996;271:33376–81. doi: 10.1074/jbc.271.52.33376.PubMedCrossRefGoogle Scholar
  23. 23.
    Dorfman DM, Shahsafaei A, Nadler LM, Freeman GJ. The leukocyte semaphorin CD100 is expressed in most T-cell, but few B-cell, non-Hodgkin’s lymphomas. Am J Pathol. 1998;153:255–62.PubMedGoogle Scholar
  24. 24.
    Delaire S, Elhabazi A, Bensussan A, Boumsell L. CD100 is a leukocyte semaphorin. Cell Mol Life Sci. 1998;54:1265–76. doi: 10.1007/s000180050252.PubMedCrossRefGoogle Scholar
  25. 25.
    Shi W, Kumanogoh A, Watanabe C, Uchida J, Wang X, Yasui T, et al. The class IV semaphorin CD100 plays nonredundant roles in the immune system: defective B and T cell activation in CD100-deficient mice. Immunity 2000;13:633–42. doi: 10.1016/S1074-7613(00)00063-7.PubMedCrossRefGoogle Scholar
  26. 26.
    Oinuma I, Ishikawa Y, Katoh H, Negishi M. The semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras. Science 2004;305:862–5. doi: 10.1126/science.1097545.PubMedCrossRefGoogle Scholar
  27. 27.
    Adachi T, Flaswinkel H, Yakura H, Reth M, Tsubata T. The B cell surface protein CD72 recruits the tyrosine phosphatase SHP-1 upon tyrosine phosphorylation. J Immunol. 1998;160:4662–5.PubMedGoogle Scholar
  28. 28.
    Parnes JR, Pan C. CD72, a negative regulator of B-cell responsiveness. Immunol Rev. 2000;176:75–85. doi: 10.1034/j.1600-065X.2000.00608.x.PubMedCrossRefGoogle Scholar
  29. 29.
    Pan C, Baumgarth N, Parnes JR. CD72-deficient mice reveal nonredundant roles of CD72 in B cell development and activation. Immunity 1999;11:495–506. doi: 10.1016/S1074-7613(00)80124-7.PubMedCrossRefGoogle Scholar
  30. 30.
    Kumanogoh A, Kikutani H. The CD100-CD72 interaction: a novel mechanism of immune regulation. Trends Immunol. 2001;22:670–6. doi: 10.1016/S1471-4906(01)02087-7.PubMedCrossRefGoogle Scholar
  31. 31.
    Niiro H, Clark EA. Regulation of B-cell fate by antigen-receptor signals. Nat Rev Immunol. 2002;2:945–56. doi: 10.1038/nri955.PubMedCrossRefGoogle Scholar
  32. 32.
    Kumanogoh A, Shikina T, Watanabe C, Takegahara N, Suzuki K, Yamamoto M, et al. Requirement for CD100-CD72 interactions in fine-tuning of B-cell antigen receptor signaling and homeostatic maintenance of the B-cell compartment. Int Immunol. 2005;17:1277–82. doi: 10.1093/intimm/dxh307.PubMedCrossRefGoogle Scholar
  33. 33.
    Samardzic T, Marinkovic D, Danzer CP, Gerlach J, Nitschke L, Wirth T. Reduction of marginal zone B cells in CD22-deficient mice. Eur J Immunol. 2002;32:561–7. doi: 10.1002/1521-4141(200202)32:2<561::AID-IMMU561>3.0.CO;2-H.PubMedCrossRefGoogle Scholar
  34. 34.
    Lopes-Carvalho T, Kearney JF. Development and selection of marginal zone B cells. Immunol Rev. 2004;197:192–205. doi: 10.1111/j.0105-2896.2004.0112.x.PubMedCrossRefGoogle Scholar
  35. 35.
    Li DH, Winslow MM, Cao TM, Chen AH, Davis CR, Mellins ED, et al. Modulation of peripheral B cell tolerance by CD72 in a murine model. Arthritis Rheum. 2008;58:3192–204. doi: 10.1002/art.23812.PubMedCrossRefGoogle Scholar
  36. 36.
    Ishida I, Kumanogoh A, Suzuki K, Akahani S, Noda K, Kikutani H. Involvement of CD100, a lymphocyte semaphorin, in the activation of the human immune system via CD72: implications for the regulation of immune and inflammatory responses. Int Immunol. 2003;15:1027–34. doi: 10.1093/intimm/dxg098.PubMedCrossRefGoogle Scholar
  37. 37.
    Kumanogoh A, Suzuki K, Ch’ng E, Watanabe C, Marukawa S, Takegahara N, et al. Requirement for the lymphocyte semaphorin, CD100, in the induction of antigen-specific T cells and the maturation of dendritic cells. J Immunol. 2002;169:1175–81.PubMedGoogle Scholar
  38. 38.
    Li M, O’Sullivan KM, Jones LK, Semple T, Kumanogoh A, Kikutani H, et al. CD100 enhances dendritic cell and CD4+ cell activation leading to pathogenetic humoral responses and immune complex glomerulonephritis. J Immunol. 2006;177:3406–12.PubMedGoogle Scholar
  39. 39.
    Wang X, Kumanogoh A, Watanabe C, Shi W, Yoshida K, Kikutani H. Functional soluble CD100/Sema4D released from activated lymphocytes: possible role in normal and pathologic immune responses. Blood 2001;97:3498–504. doi: 10.1182/blood.V97.11.3498.PubMedCrossRefGoogle Scholar
  40. 40.
    Watanabe C, Kumanogoh A, Shi W, Suzuki K, Yamada S, Okabe M, et al. Enhanced immune responses in transgenic mice expressing a truncated form of the lymphocyte semaphorin CD100. J Immunol. 2001;167:4321–8.PubMedGoogle Scholar
  41. 41.
    Giraudon P, Vincent P, Vuaillat C, Verlaeten O, Cartier L, Marie-Cardine A, et al. Semaphorin CD100 from activated T lymphocytes induces process extension collapse in oligodendrocytes and death of immature neural cells. J Immunol. 2004;172:1246–55.PubMedGoogle Scholar
  42. 42.
    Kumanogoh A, Shikina T, Suzuki K, Uematsu S, Yukawa K, Kashiwamura S, et al. Nonredundant roles of Sema4A in the immune system: defective T cell priming and Th1/Th2 regulation in Sema4A-deficient mice. Immunity 2005;22:305–16. doi: 10.1016/j.immuni.2005.01.014.PubMedCrossRefGoogle Scholar
  43. 43.
    Rice DS, Huang W, Jones HA, Hansen G, Ye GL, Xu N, et al. Severe retinal degeneration associated with disruption of semaphorin 4A. Invest Ophthalmol Vis Sci. 2004;45:2767–77. doi: 10.1167/iovs.04-0020.PubMedCrossRefGoogle Scholar
  44. 44.
    McIntire JJ, Umetsu SE, Akbari O, Potter M, Kuchroo VK, Barsh GS, et al. Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family. Nat Immunol. 2001;2:1109–16. doi: 10.1038/ni739.PubMedCrossRefGoogle Scholar
  45. 45.
    Kuchroo VK, Dardalhon V, Xiao S, Anderson AC. New roles for TIM family members in immune regulation. Nat Rev Immunol. 2008;8:577–80. doi: 10.1038/nri2366.PubMedCrossRefGoogle Scholar
  46. 46.
    Meyers JH, Sabatos CA, Chakravarti S, Kuchroo VK. The TIM gene family regulates autoimmune and allergic diseases. Trends Mol Med. 2005;11:362–9. doi: 10.1016/j.molmed.2005.06.008.PubMedCrossRefGoogle Scholar
  47. 47.
    Mizui M, Shikina T, Arase H, Suzuki K, Yasui T, Rennert PD, et al. Bimodal regulation of T cell-mediated immune responses by TIM-4. Int Immunol. 2008;20:695–708. doi: 10.1093/intimm/dxn029.PubMedCrossRefGoogle Scholar
  48. 48.
    Kuchroo VK, Umetsu DT, DeKruyff RH, Freeman GJ. The TIM gene family: emerging roles in immunity and disease. Nat Rev Immunol. 2003;3:454–62. doi: 10.1038/nri1111.PubMedCrossRefGoogle Scholar
  49. 49.
    Chakravarti S, Sabatos CA, Xiao S, Illes Z, Cha EK, Sobel RA, et al. Tim-2 regulates T helper type 2 responses and autoimmunity. J Exp Med. 2005;202:437–44. doi: 10.1084/jem.20050308.PubMedCrossRefGoogle Scholar
  50. 50.
    Rennert PD, Ichimura T, Sizing ID, Bailly V, Li Z, Rennard R, et al. T cell, Ig domain, mucin domain-2 gene-deficient mice reveal a novel mechanism for the regulation of Th2 immune responses and airway inflammation. J Immunol. 2006;177:4311–21.PubMedGoogle Scholar
  51. 51.
    Yamada A, Kubo K, Takeshita T, Harashima N, Kawano K, Mine T, et al. Molecular cloning of a glycosylphosphatidylinositol-anchored molecule CDw108. J Immunol. 1999;162:4094–100.PubMedGoogle Scholar
  52. 52.
    Mine T, Harada K, Matsumoto T, Yamana H, Shirouzu K, Itoh K, et al. CDw108 expression during T-cell development. Tissue Antigens. 2000;55:429–36. doi: 10.1034/j.1399-0039.2000.550505.x.PubMedCrossRefGoogle Scholar
  53. 53.
    Tamagnone L, Comoglio PM. Signalling by semaphorin receptors: cell guidance and beyond. Trends Cell Biol. 2000;10:377–83. doi: 10.1016/S0962-8924(00)01816-X.PubMedCrossRefGoogle Scholar
  54. 54.
    Scott GA, McClelland LA, Fricke AF. Semaphorin 7a promotes spreading and dendricity in human melanocytes through beta1-integrins. J Invest Dermatol. 2008;128:151–61. doi: 10.1038/sj.jid.5700974.PubMedCrossRefGoogle Scholar
  55. 55.
    Pasterkamp RJ, Peschon JJ, Spriggs MK, Kolodkin AL. Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature 2003;424:398–405. doi: 10.1038/nature01790.PubMedCrossRefGoogle Scholar
  56. 56.
    Suzuki K, Okuno T, Yamamoto M, Pasterkamp RJ, Takegahara N, Takamatsu H, et al. Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin. Nature 2007;446:680–4. doi: 10.1038/nature05652.PubMedCrossRefGoogle Scholar
  57. 57.
    Holmes S, Downs AM, Fosberry A, Hayes PD, Michalovich D, Murdoch P, et al. Sema7A is a potent monocyte stimulator. Scand J Immunol. 2002;56:270–5. doi: 10.1046/j.1365-3083.2002.01129.x.PubMedCrossRefGoogle Scholar
  58. 58.
    Alderson MR, Armitage RJ, Tough TW, Strockbine L, Fanslow WC, Spriggs MK. CD40 expression by human monocytes: regulation by cytokines and activation of monocytes by the ligand for CD40. J Exp Med. 1993;178:669–74. doi: 10.1084/jem.178.2.669.PubMedCrossRefGoogle Scholar
  59. 59.
    Toyofuku T, Zhang H, Kumanogoh A, Takegahara N, Yabuki M, Harada K, et al. Guidance of myocardial patterning in cardiac development by Sema6D reverse signalling. Nat Cell Biol. 2004;6:1204–11. doi: 10.1038/ncb1193.PubMedCrossRefGoogle Scholar
  60. 60.
    Wong AW, Brickey WJ, Taxman DJ, van Deventer HW, Reed W, Gao JX, et al. CIITA-regulated plexin-A1 affects T-cell-dendritic cell interactions. Nat Immunol. 2003;4:891–8. doi: 10.1038/ni960.PubMedCrossRefGoogle Scholar
  61. 61.
    Takegahara N, Takamatsu H, Toyofuku T, Tsujimura T, Okuno T, Yukawa K, et al. Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nat Cell Biol. 2006;8:615–22. doi: 10.1038/ncb1416.PubMedCrossRefGoogle Scholar
  62. 62.
    Tomasello E, Desmoulins PO, Chemin K, Guia S, Cremer H, Ortaldo J, et al. Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice. Immunity 2000;13:355–64. doi: 10.1016/S1074-7613(00)00035-2.PubMedCrossRefGoogle Scholar
  63. 63.
    Zompi S, Hamerman JA, Ogasawara K, Schweighoffer E, Tybulewicz VL, Di Santo JP, et al. NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases. Nat Immunol. 2003;4:565–72. doi: 10.1038/ni930.PubMedCrossRefGoogle Scholar
  64. 64.
    Bakker AB, Hoek RM, Cerwenka A, Blom B, Lucian L, McNeil T, et al. DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming. Immunity 2000;13:345–53. doi: 10.1016/S1074-7613(00)00034-0.PubMedCrossRefGoogle Scholar
  65. 65.
    Kaifu T, Nakahara J, Inui M, Mishima K, Momiyama T, Kaji M, et al. Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice. J Clin Invest. 2003;111:323–32.PubMedGoogle Scholar
  66. 66.
    O’Connor BP, Eun SY, Ye Z, Zozulya AL, Lich JD, Moore CB, et al. Semaphorin 6D regulates the late phase of CD4+ T cell primary immune responses. Proc Natl Acad Sci USA. 2008;105:13015–20. doi: 10.1073/pnas.0803386105.PubMedCrossRefGoogle Scholar
  67. 67.
    Comeau MR, Johnson R, DuBose RF, Petersen M, Gearing P, VandenBos T, et al. A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR. Immunity 1998;8:473–82. doi: 10.1016/S1074-7613(00)80552-X.PubMedCrossRefGoogle Scholar
  68. 68.
    Walzer T, Galibert L, Comeau MR, De Smedt T. Plexin C1 engagement on mouse dendritic cells by viral semaphorin A39R induces actin cytoskeleton rearrangement and inhibits integrin-mediated adhesion and chemokine-induced migration. J Immunol. 2005;174:51–9.PubMedGoogle Scholar
  69. 69.
    Walzer T, Galibert L, De Smedt T. Poxvirus semaphorin A39R inhibits phagocytosis by dendritic cells and neutrophils. Eur J Immunol. 2005;35:391–8. doi: 10.1002/eji.200425669.PubMedCrossRefGoogle Scholar
  70. 70.
    Lepelletier Y, Moura IC, Hadj-Slimane R, Renand A, Fiorentino S, Baude C, et al. Immunosuppressive role of semaphorin-3A on T cell proliferation is mediated by inhibition of actin cytoskeleton reorganization. Eur J Immunol. 2006;36:1782–93. doi: 10.1002/eji.200535601.PubMedCrossRefGoogle Scholar
  71. 71.
    Moretti S, Procopio A, Lazzarini R, Rippo MR, Testa R, Marra M, et al. Semaphorin3A signaling controls Fas (CD95)-mediated apoptosis by promoting Fas translocation into lipid rafts. Blood 2008;111:2290–9. doi: 10.1182/blood-2007-06-096529.PubMedCrossRefGoogle Scholar
  72. 72.
    Yamamoto M, Suzuki K, Okuno T, Ogata T, Takegahara N, Takamatsu H, et al. Plexin-A4 negatively regulates T lymphocyte responses. Int Immunol. 2008;20:413–20. doi: 10.1093/intimm/dxn006.PubMedCrossRefGoogle Scholar
  73. 73.
    Suto F, Tsuboi M, Kamiya H, Mizuno H, Kiyama Y, Komai S, et al. Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers. Neuron 2007;53:535–47. doi: 10.1016/j.neuron.2007.01.028.PubMedCrossRefGoogle Scholar
  74. 74.
    Tordjman R, Lepelletier Y, Lemarchandel V, Cambot M, Gaulard P, Hermine O, et al. A neuronal receptor, neuropilin-1, is essential for the initiation of the primary immune response. Nat Immunol. 2002;3:477–82.PubMedGoogle Scholar
  75. 75.
    Bruder D, Probst-Kepper M, Westendorf AM, Geffers R, Beissert S, Loser K, et al. Neuropilin-1: a surface marker of regulatory T cells. Eur J Immunol. 2004;34:623–30. doi: 10.1002/eji.200324799.PubMedCrossRefGoogle Scholar
  76. 76.
    Hill JA, Feuerer M, Tash K, Haxhinasto S, Perez J, Melamed R, et al. Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 2007;27:786–800.PubMedCrossRefGoogle Scholar
  77. 77.
    Sarris M, Andersen KG, Randow F, Mayr L, Betz AG. Neuropilin-1 expression on regulatory T cells enhances their interactions with dendritic cells during antigen recognition. Immunity 2008;28:402–13. doi: 10.1016/j.immuni.2008.01.012.PubMedCrossRefGoogle Scholar
  78. 78.
    Delaire S, Billard C, Tordjman R, Chedotal A, Elhabazi A, Bensussan A, et al. Biological activity of soluble CD100. II. Soluble CD100, similarly to H-SemaIII, inhibits immune cell migration. J Immunol. 2001;166:4348–54.PubMedGoogle Scholar
  79. 79.
    Zhu L, Bergmeier W, Wu J, Jiang H, Stalker TJ, Cieslak M, et al. Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Proc Natl Acad Sci USA. 2007;104:1621–6. doi: 10.1073/pnas.0606344104.PubMedCrossRefGoogle Scholar
  80. 80.
    Mizrahi S, Markel G, Porgador A, Bushkin Y, Mandelboim O. CD100 on NK cells enhance IFNgamma secretion and killing of target cells expressing CD72. PLoS One. 2007;2:e818. doi: 10.1371/journal.pone.0000818.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Masayuki Mizui
    • 1
    • 3
  • Atsushi Kumanogoh
    • 2
    • 3
  • Hitoshi Kikutani
    • 1
    • 3
  1. 1.Department of Molecular Immunology, Research Institute for Microbial DiseasesOsaka UniversitySuitaJapan
  2. 2.Department of Immunopathology, Research Institute for Microbial DiseasesOsaka UniversitySuitaJapan
  3. 3.WPI Immunology Frontier Research CenterOsaka UniversitySuitaJapan

Personalised recommendations