Advertisement

Neuro-Immune Crosstalk in CNS Diseases

  • Martin Kerschensteiner
  • Edgar Meinl
  • Reinhard Hohlfeld
Chapter
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 51)

Abstract

Immune cells infiltrate the central nervous system (CNS) in many neurological diseases, with a primary or secondary inflammatory component. In the CNS, immune cells employ shared mediators to promote crosstalk with neuronal cells. The net effect of this neuro-immune crosstalk critically depends on the context of the interaction. It has long been established that inflammatory reactions in the CNS can cause or augment tissue injury in many experimental paradigms. However, emerging evidence suggests that in other paradigms inflammatory cells can contribute to neuroprotection and repair. This dual role of CNS inflammation is also reflected on the molecular level as it is becoming increasingly clear that immune cells can release both neurodestructive and neuroprotective molecules into CNS lesions. It is thus the balance between destructive and protective factors that ultimately determines the net result of the neuro-immune interaction.

Keywords

Multiple Sclerosis Neurotrophic Factor Experimental Autoimmune Encephalomyelitis Myelin Basic Protein Central Nervous System Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors have been supported by the Deutsche Forschungsgemeinschaft (Emmy Noether Programm and SFB 571), Hermann and Lilly Schilling Foundation; Max Planck Society and Verein “Therapieforschung für Multiple Sklerose Kranke e.V”. The authors thank Markus Krumbholz for the help with figures. This chapter is reprinted, with permission from the publisher, from our recent review article (Kerschensteiner, M., Meinl E., Hohlfeld R. (in press) Neuro-immune crosstalk in CNS disease. Neuroscience).

References

  1. Airaksinen MS, Saarma M (2002) The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci 3:383–394PubMedGoogle Scholar
  2. Allen CD, Ansel KM, Low C, Lesley R, Tamamura H, Fujii N, Cyster JG (2004) Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5. Nat Immunol 5:943–952PubMedGoogle Scholar
  3. Alt C, Laschinger M, Engelhardt B (2002) Functional expression of the lymphoid chemokines CCL19 (ELC) and CCL 21 (SLC) at the blood-brain barrier suggests their involvement in G-protein-dependent lymphocyte recruitment into the central nervous system during experimental autoimmune encephalomyelitis. Eur J Immunol 32:2133–2144PubMedGoogle Scholar
  4. Arancio O, Chao MV (2007) Neurotrophins, synaptic plasticity and dementia. Curr Opin Neurobiol 17:325–330PubMedGoogle Scholar
  5. Bayas A, Kruse N, Moriabadi NF, Weber F, Hummel V, Wohleben G, Gold R, Toyka KV, Rieckmann P (2003) Modulation of cytokine mRNA expression by brain-derived neurotrophic factor and nerve-growth factor in human immune cells. Neurosci Lett 335:155–158PubMedGoogle Scholar
  6. Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ (1997) A new class of membrane-bound chemokine with a CX3C motif. Nature 385:640–644PubMedGoogle Scholar
  7. Besser M, Wank R (1999) Cutting edge: clonally restricted production of the neurotrophins brain-derived neurotrophic factor and neurotrophin-3 mRNA by human immune cells and Th1/Th2-polarized expression of their receptors. J Immunol 162:6303–6306PubMedGoogle Scholar
  8. Bhattacharyya BJ, Banisadr G, Jung H, Ren D, Cronshaw DG, Zou Y, Miller RJ (2008) The chemokines stromal cell-derived factor-1 regulates GABAergic inputs to neuronal progenitors in the postnatal dentate gyrus. J Neurosci 28:6720–6730PubMedCentralPubMedGoogle Scholar
  9. Bitsch A, Schuchardt J, Bunkowski S, Kuhlmann T, Brück W (2000) Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain 123:1174–1183PubMedGoogle Scholar
  10. Bjartmar C, Kidd G, Mörk S, Rudick R, Trapp BD (2000) Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 48:893–901PubMedGoogle Scholar
  11. Bjartmar C, Trapp BD (2001) Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences. Curr Opin Neurol 14:271–278PubMedGoogle Scholar
  12. Braun A, Lommatzsch M, Mannsfeldt A, Neuhaus-Steinmetz U, Fischer A, Schnoy N, Lewin GR, Renz H (1999) Cellular sources of enhanced brain-derived neurotrophic factor production in a mouse model of allergic inflammation. Am J Respir Cell Mol Biol 21:537–546PubMedGoogle Scholar
  13. Butler MP, O’Connor JJ, Moynagh PN (2004) Dissection of tumor-necrosis factor-alpha inhibition of long-term potentiation (LTP) reveals a p38 mitogen-activated protein kinase-dependent mechanism which maps to early- but not late-phase LTP. Neuroscience 124:319–326PubMedGoogle Scholar
  14. Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, Kidd G, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S, Lira SA, Littman DR, Ransohoff RM (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917–924PubMedGoogle Scholar
  15. Cho J, Gruol DL (2008) The chemokines CCL2 activates p38 mitogen-activated protein kinase pathway in cultured rat hippocampal cells. J Neuroimmunol 199:94–103PubMedCentralPubMedGoogle Scholar
  16. Chopp M, Li Y, Jiang N, Zhang RL, Prostak J (1996) Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain. J Cereb Blood Flow Metab 16:578–584PubMedGoogle Scholar
  17. Confavreux C, Vukusic S, Moreau T, Adeleine P (2000) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343:1430–1438PubMedGoogle Scholar
  18. Connolly ES Jr, Winfree CJ, Springer TA, Naka Y, Liao H, Yan SD, Stern DM, Solomon RA, Gutierrez-Ramos JC, Pinsky DJ (1996) Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke. J Clin Invest 97:209–216PubMedCentralPubMedGoogle Scholar
  19. Cumiskey D, Pickering M, O’Connor JJ (2007) Interleukin-18 mediated inhibition of LTP in the rat dentate gyrus is attenuated in the presence of mGluR antagonists. Neurosci Lett 412:206–210PubMedGoogle Scholar
  20. Dirnagl U, Klehmet J, Braun JS, Harms H, Meisel C, Ziemssen T, Prass K, Meisel A (2007) Stroke-induced immunodepression. Experimental evidence and clinical relevance. Stroke 38:770–773PubMedGoogle Scholar
  21. Ehrhard PB, Erb P, Graumann U, Otten U (1993) Expression of nerve growth factor and nerve growth factor receptor tyrosine kinase Trk in activated CD4-positive T-cell clones. Proc Natl Acad Sci USA 90:10984–10988PubMedCentralPubMedGoogle Scholar
  22. Enlimomab Acute Stroke Trial Investigators (2001) Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology 57:1428–1434Google Scholar
  23. Flügel A, Matsumuro K, Neumann H, Klinkert WE, Birnbacher R, Lassmann H, Otten U, Wekerle H (2001) Anti-inflammatory activity of nerve growth factor in experimental autoimmune encephalomyelitis: inhibition of monocyte transendothelial migration. Eur J Immunol 31:11–22PubMedGoogle Scholar
  24. Gartner A, Polnau D, Staiger V, Sciarretta C, Minichiello L, Thoenen H, Bonhoeffer T, Korte M (2006) Hippocampal long-term potentiation is supported by presynaptic and postsynaptic tyrosine receptor kinase B-mediated phospholipase Cγ signaling. J Neurosci 26:3496–3504PubMedGoogle Scholar
  25. Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964PubMedGoogle Scholar
  26. Hammarberg H, Lidman O, Lundberg C, Eltayeb SY, Gielen AW, Muhallab S, Svenningsson A, Lindå H, van Der Meide PH, Cullheim S, Olsson T, Piehl F (2000) Neuroprotection by encephalomyelitis: rescue of mechanically injured neurons and neurotrophin production by CNS-infiltrating T and natural killer cells. J Neurosci 20:5283–5291PubMedGoogle Scholar
  27. Harrison JK, Jiang Y, Chen S, Xia Y, Maciejewski D, McNamara RK, Streit WJ, Salafranca MN, Adhikari S, Thompson DA, Botti P, Bacon KB, Feng L (1998) Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglial. Proc Natl Acad Sci USA 95:10896–10901PubMedCentralPubMedGoogle Scholar
  28. Hauben E, Butovsky O, Nevo U, Yoles E, Moalem G, Agranov E, Mor F, Leibowitz-Amit R, Pevsner E, Akselrod S, Neeman M, Cohen IR, Schwartz M (2000) Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. J Neurosci 20:6421–6430PubMedGoogle Scholar
  29. Hauser SL, Oksenberg JR (2006) The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 52:61–76PubMedGoogle Scholar
  30. Hendrix S, Nitsch R (2007) The role of T helper cells in neuroprotection and regeneration. J Neuroimmunol 184:100–112PubMedGoogle Scholar
  31. Hohlfeld R, Wekerle H (2004) Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: from pipe dreams to (therapeutic) pipelines. Proc Natl Acad Sci USA 101:14599–14606PubMedCentralPubMedGoogle Scholar
  32. Huang D, Shi FD, Jung S, Pien GC, Wang J, Salazar-Mather TP, He TT, Weaver JT, Ljunggren HG, Biron CA, Littman DR, Ransohoff RM (2006) The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system. FASEB J 20:896–905PubMedGoogle Scholar
  33. Huising MO, Stet RJ, Kruiswijk CP, Savelkoul HF, Lidy Verburg-van Kemenade BM (2003) Molecular evolution of CXC chemokines: extant CXC chemokines originate from the CNS. Trends Immunol 24:307–313PubMedGoogle Scholar
  34. Hulshof S, van Haastert ES, Kuipers HF, van den Elsen PJ, De Groot CJ, van der Valk P, Ravid R, Biber K (2003) CX3CL1 and CX3CR1 expression in human brain tissue: noninflammatory control versus multiple sclerosis.” J Neuropathol Exp Neurol 62:899–907PubMedGoogle Scholar
  35. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O (1997) Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 91:521–530PubMedGoogle Scholar
  36. Jiang Y, Chen G, Zhang Y, Lu L, Liu S, Cao X (2007) Nerve growth factor promotes the TLR4 signaling-induced maturation of human dendritic cells in vitro through inducible p75NTR 1. J Immunol 179:6297–6304PubMedGoogle Scholar
  37. Jones TB, Basso DM, Sodhi A, Pan JZ, Hart RP, MacCallum RC, Lee S, Whitacre CC, Popovich PG (2002) Pathological CNS autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy. J Neurosci 22:2690–2700PubMedGoogle Scholar
  38. Jones TB, Ankeny DP, Guan Z, McGaughy V, Fisher LC, Basso DM, Popovich PG (2004) Passive or active immunization with myelin basic protein impairs neurological function and exacerbates neuropathology after spinal cord injury in rats. J Neurosci 24:3752–3761PubMedGoogle Scholar
  39. Kalled SL (2006) Impact of the BAFF/BR3 axis on B cell survival, germinal center maintenance and antibody production. Semin Immunol 18:290–296PubMedGoogle Scholar
  40. Kallo T, Nagata T, Yamamoto S, Okamura H, Nishizaki T (2004) Interleukin-18 stimulates synaptically released glutamate and enhances post-synaptic AMPA receptor responses in the CA1 region of mouse hippocampal slices. Brain Res 25:190–193Google Scholar
  41. Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R (1999) Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation. J Exp Med 189:865–870PubMedCentralPubMedGoogle Scholar
  42. Kerschensteiner M, Stadelmann C, Dechant G, Wekerle H, Hohlfeld R (2003) Neurotrophic cross-talk between the nervous and immune systems: implications for neurological diseases. Ann Neurol 53:292–304PubMedGoogle Scholar
  43. Kieseier BC, Wiendl H, Hemmer B, Hartung HP (2007) Treatment and treatment trials in multiple sclerosis. Curr Opin Neurol 20:286–293PubMedGoogle Scholar
  44. Killestein J, Polman CH (2005) Current trials in multiple sclerosis: established evidence and future hopes. Curr Opin Neurol 18:253–260PubMedGoogle Scholar
  45. Kipnis J, Yoles E, Porat Z, Cohen A, Mor F, Sela M, Cohen IR, Schwartz M (2000) T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: possible therapy for optic neuropathies. Proc Natl Acad Sci USA 97:7446–7451PubMedCentralPubMedGoogle Scholar
  46. Kishimoto T (2005) Interleukin-6: from basic science to medicine – 40 years in immunology. Ann Rev Immunol 23:1–21Google Scholar
  47. Kivisäkk P, Mahad DJ, Callahan MK, Trebst C, Tucky B, Wei T, Wu L, Baekkevold ES, Lassmann H, Staugaitis SM, Campbell JJ, Ransohoff RM (2003) Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci USA 100:8389–8394PubMedCentralPubMedGoogle Scholar
  48. Knoblach SM, Fan L, Faden AI. (1999) Early neuronal expression of tumor necrosis factor-alpha after experimental brain injury contributes to neurological impairment. J Neuroimmunol 95:115–125PubMedGoogle Scholar
  49. Kornek B, Storch MK, Weissert R, Wallstroem E, Stefferl A, Olsson T, Linington C, Schmidbauer M, Lassmann H (2000) Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol 157:267–276PubMedCentralPubMedGoogle Scholar
  50. Kucia M, Jankowski K, Reca R, Wysoczynski M, Bandura L, Allendorf DJ, Zhang J, Ratajczak J, Ratajczak MZ (2004) CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol 35:233–245PubMedGoogle Scholar
  51. Kuhlmann T, Remington L, Cognet I, Bourbonniere L, Zehntner S, Guihot F, Herman A, Guay-Giroux A, Antel JP, Owens T, Gauchat JF (2006) Continued administration of ciliary neurotrophic factor protects mice from inflammatory pathology in experimental autoimmune encephalomyelitis. Am J Pathol 169:584–598PubMedCentralPubMedGoogle Scholar
  52. Krams M, Lees KR, Hacke W, Grieve AP, Orgogozo JM, Ford GAASTIN Study Investigators(2003). Acute stroke therapy by inhibition of neutrophils (ASTIN): an adaptive dose-response study of UK-279 276 in acute ischemic stroke. Stroke 34:2543–2548PubMedGoogle Scholar
  53. Krumbholz M, Theil D, Derfuss T, Rosenwald A, Schrader F, Monoranu CM, Kalled SL, Hess DM, Serafini B, Aloisi F, Wekerle H, Hohlfeld R, Meinl E (2005) BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J Exp Med 201:195–200PubMedCentralPubMedGoogle Scholar
  54. Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisäkk P, Ransohoff RM, Hofbauer M, Farina C, Derfuss T, Hartle C, Newcombe J, Hohlfeld R, Meinl E (2006) Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 129:200–211PubMedGoogle Scholar
  55. Krumbholz M, Theil D, Steinmeyer F, Cepok S, Hemmer B, Hofbauer M, Farina C, Derfuss T, Junker A, Arzberger T, Sinicina I, Hartle C, Newcombe J, Hohlfeld R, Meinl E (2007) CCL19 is constitutively expressed in the CNS, up-regulated in neuroinflammation, active and also inactive multiple sclerosis lesions. J Neuroimmunol 190:72–79PubMedGoogle Scholar
  56. Kutzelnigg A, Lucchinetti CF, Stadelmann C, Brück W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128:2705–2712PubMedGoogle Scholar
  57. Lauro C, Catalano M, Trettel F, Mainiero F, Ciotti MT, Eusebi F, Limatola C (2006) The chemokines CX3CL1 reduces migration and increases adhesion of neurons with mechanisms dependent on the beta1 integrin subunit. J Immunol 177:7599–7606PubMedGoogle Scholar
  58. Lewin GR, Barde YA (1996) Physiology of the neurotrophins. Annu Rev Neurosci 19:289–317PubMedGoogle Scholar
  59. Li G, Adesnik H, Li J, Long J, Nicoll RA, Rubenstein JL, Pleasure SJ (2008) Regional distribution of cortical interneurons and development of inhibitory tone are regulated by Cxcl12/Cxcr4 signaling. J Neurosci 28:1085–1098PubMedCentralPubMedGoogle Scholar
  60. Li M, Ransohoff RM (2008) Multiple roles of chemokine CXCL12 in the central nervous system: a migration from immunology to neurobiology. Prog Neurobiol 4:116–131Google Scholar
  61. Liew FY (2002) T (H)1 and T(H)2 cells: a historical perspective. Nat Rev Immunol 2:55–60PubMedGoogle Scholar
  62. Linker R, Lee DH, Siglienti I, Gold R (2007) Is there a role for neurotrophins in the pathology of multiple sclerosis. J Neurol 254:I/33–I/40Google Scholar
  63. Linker R, Kruse N, Israel S, Wei T, Seubert S, Hombach A, Holtmann B, Luhder F, Ransohoff RM, Sendtner M, Gold R (2008) Leukemia inhibitory factor deficiency modulates the immune response and limits autoimmune demyelination: a new role for neurotrophic cytokines in neuroinflammation. J Immunol 180:2204–2213PubMedGoogle Scholar
  64. Liu L, Li Y, Van Eldik LJ, Griffin WS, Barger SW (2005) S100B-induced microglial and neuronal IL-1 expression is mediated by cell type-specific transcription factors. J Neurochem 92:546–553PubMedGoogle Scholar
  65. Losseff NA, Wang L, Lai HM, Yoo DS, Gawne-Cain ML, McDonald WI, Miller DH, Thompson AJ (1996) Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. Brain 119:2009–2019PubMedGoogle Scholar
  66. Lu B, Pang PT, Woo NH (2005) The yin and yang of neurotrophin action. Nat Rev Neurosci 6:603–614PubMedGoogle Scholar
  67. Lu D, Goussev A, Chen J, Pannu P, Li Y, Mahmood A, Chopp M (2004) Atorvastatin reduces neurological deficits and increases synaptogenesis, angiogenesis and neuronal survival in rats subjected to traumatic brain injury. J Neurotrauma 21:21–32PubMedGoogle Scholar
  68. Mantovani A, Sica A, Locati M (2005) Macrophage Polarization comes of age. Immunity 23:344–346PubMedGoogle Scholar
  69. Manz RA, Hauser AE, Hiepe F, Radbruch A (2005) Maintenance of serum antibody levels. Annu Rev Immunol 23:367–386PubMedGoogle Scholar
  70. Maroder M, Bellavia D, Meco D, Napolitano M, Stigliano A, Alesse E, Vacca A, Frati L, Gulinno A, Screpanti I (1996) Expression of trkB neurotrophin receptor during T cell development. Role of brain derived neurotrophic factor in immature thymocyte survival. J Immunol 157:2864–2872PubMedGoogle Scholar
  71. McAllister AK, Katz LC, Lo DC (1999) Neurotrophins and synaptic plasticity. Ann Rev Neurosci 22:295–318PubMedGoogle Scholar
  72. Meinl E, Krumbholz M, Hohlfeld R (2006) B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation. Ann Neurol 59:880–892PubMedGoogle Scholar
  73. Miller DH, Leary SM (2007) Primary-progressive multiple sclerosis. Lancet Neurol 6:903–912PubMedGoogle Scholar
  74. Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen IR, Schwartz M. (1999) Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 5:49–55PubMedGoogle Scholar
  75. Moalem G, Gdalyahu A, Shani Y, Otten U, Lazarovici P, Cohen IR, Schwartz M (2000) Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J Autoimmun 15:331–345PubMedGoogle Scholar
  76. Mulcahy NJ, Ross J, Rothwell NJ, Loddick SA (2003) Delayed administration of interleukin-1 receptor antagonist protects against transient cerebral ischemia in the rat. Br J Pharmacol 140:471–476PubMedCentralPubMedGoogle Scholar
  77. Nagappan G, Woo NH, Lu B (2008) Ama “zinc” link between TrkB transactivation and synaptic plasticity. Neuron 57:477–479PubMedGoogle Scholar
  78. Neumann H, Schmidt H, Wilharm E, Behrens L, Wekerle H (1997) Interferon gamma gene expression in sensory neurons: evidence for autocrine gene regulation. J Exp Med 186:2023–2031PubMedCentralPubMedGoogle Scholar
  79. Neumann H, Schweigreiter R, Yamashita T, Rosenkranz K, Wekerle H, Barde YA (2002) Tumor necrosis factor inhibits neurite outgrowth and branch formation of hippocampal neurons by a rho-dependent mechanism. J Neurosci 22:854–862PubMedGoogle Scholar
  80. Neumann H, Misgeld T, Matsumuro K, Wekerle H (1998) Neurotrophins inhibit major histocompatibility class II inducibility of microglia: involvement of the p75 neurotrophin receptor. Proc Natl Acad Sci USA 95:5779–5784PubMedCentralPubMedGoogle Scholar
  81. Newman TA, Woolley ST, Hughes PM, Sibson NR, Anthony DC, Perry VH (2001) T-cell- and macrophage-mediated axon damage in the absence of a CNS- specific immune response: involvement of metalloproteinases. Brain 124:2203–2214PubMedGoogle Scholar
  82. Ohshima Y, Kubo T, Koyama R, Ueno M, Nakagawa M, Yamashita T (2008) Regulation of axonal elongation and pathfinding from the entorhinal cortex to the dentate gyrus in the hippocampus by the cytokine stromal cell-derived factor 1alpha. J Neurosci 28:8344–8353PubMedGoogle Scholar
  83. Omari KM, John GR, Sealfon SC, Raine CS (2005) CXC chemokine receptors on human oligodendrocytes: implications for multiple sclerosis. Brain 128:1003–1015PubMedGoogle Scholar
  84. Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899–910PubMedGoogle Scholar
  85. Prass K, Meisel C, Hoflich C, Braun J, Halle E, Wolf T, Ruscher K, Victorov IV, Priller J, Dirnagl U, Volk HD, Meisel A (2003) Stroke-induced immunodeficiency promotes spontanous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med 198:725–736PubMedCentralPubMedGoogle Scholar
  86. Ragozzino D, Di Angelantonio S, Trettel F, Bertollini C, Maggi L, Gross C, Charo IF, Limatola C, Eusebi F (2006) Chemokine fractalkine/CX3CL1 negatively modulates active glutamatergic synapses in rat hippocampal neurons. J Neurosci 26:10488–10498PubMedGoogle Scholar
  87. Rapalino O, Lazarov-Spiegler O, Agranov E, Velan GJ, Yoles E, Fraidakis M, Solomon A, Gepstein R, Katz A, Belkin M, Hadani M, Schwartz M (1998) Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med 4:814–821PubMedGoogle Scholar
  88. Rose CR, Blum R, Pichler B, Lepier A, Kafitz KW, Konnerth A (2003) Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells. Nature 426:74–78PubMedGoogle Scholar
  89. Serpe CJ, Kohm AP, Huppenbauer CB, Sanders VM, Jones KJ (1999) Exacerbation of facial motoneuron loss after facial nerve transection in severe combined immunodeficient (scid) mice. J Neurosci 19:RC7PubMedGoogle Scholar
  90. Sicotte M, Tsatas O, Jeong SY, Cai CQ, He Z, David S (2003) Immunization withmyelin or recombinant Nogo-66/MAG in alum promotes axon regeneration and sprouting after corticospinal tract lesions in the spinal cord. Mol Cell Neurosci 23:251–263PubMedGoogle Scholar
  91. Soriano SG, Amaravadi LS, Wang YF, Zhou H, Yu GX, Tonra JR, Fairchild-Huntress V, Fang Q, Dunmore JH, Huszar D, Pan Y. S. G. Soriano (2002) Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury. J Neuroimmunol 125:59–65PubMedGoogle Scholar
  92. Stadelmann C, Kerschensteiner M, Misgeld T, Brück W, Hohlfeld R, Lassmann H (2002) BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells. Brain 125:75–85PubMedGoogle Scholar
  93. Storch MK, Stefferl A, Brehm U, Weissert R, Wallström E, Kerschensteiner M, Olsson T, Linington C, Lassmann H (1998) Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology. Brain Pathol 8:681–694PubMedGoogle Scholar
  94. Sun JH, Yang B, Donnelly DF, Ma C, LaMotte RH (2006) MCP-1 enhances excitability of nociceptive neurons in chronically compressed dorsal root ganglia. J Neurophysiol 96:2189–2199PubMedGoogle Scholar
  95. Sunnemark D, Eltayeb S, Nilsson M, Wallström E, Lassmann H, Olsson T, Berg AL, Ericsson-Dahlstrand A (2005) CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin. J Neuroinflammation 2:17PubMedCentralPubMedGoogle Scholar
  96. Thoenen H, Sendtner M (2002) Neurotrophins: from enthusiastic expectations through sobering experiences to rational therapeutic approaches. Nat Neurosci 5S:1046–1050Google Scholar
  97. Tomac A, Lindqvist E, Lin LF, Ogren SO, Young D, Hoffer BJ, Olson L (1995) Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 373:335–339PubMedGoogle Scholar
  98. Tomac AC, Agulnick AD, Haughey N, Chang CF, Zhang Y, Bäckman C, Morales M, Mattson MP, Wang Y, Westphal H, Hoffer BJ (2002) Effects of cerebral ischemia in mice deficient in Persephin. Proc Natl Acad Sci USA 99:9521–9526PubMedCentralPubMedGoogle Scholar
  99. Torcia M, Bracci-Laudiero L, Lucibello M, Nencioni L, Labardi D, Rubartelli A, Cozzolino F, Aloe L, Garaci E (1996) Nerve growth factor is an autocrine survival factor for memory B lymphocytes. Cell 85:345–356PubMedGoogle Scholar
  100. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285PubMedGoogle Scholar
  101. Tsai HH, Frost E, To V, Robinson S, Ffrench-Constant C, Geertman R, Ransohoff RM, Miller RH (2002) The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell 110:373–383PubMedGoogle Scholar
  102. Vargas-Leal V, Bruno R, Derfuss T, Krumbholz M, Hohlfeld R, Meinl E (2005) Expression and function of glial cell line-derived neurotrophic factor family ligands and their receptors on human immune cells. J Immunol 175:2301–2308PubMedGoogle Scholar
  103. Vergote D, Butler GS, Ooms M, Cox JH, Silva C, Hollenberg MD, Jhamandas JH, Overall CM, Power C (2006) Proteolytic processing of SDF-1alpha reveals a change in receptor specificity mediating HIV-associated neurodegeneration. Proc Natl Acad Sci USA 103:19182–19187PubMedCentralPubMedGoogle Scholar
  104. Villoslada P, Hauser SL, Bartke I, Unger J, Heald N, Rosenberg D, Cheung SW, Mobley WC, Fisher S, Genain CP (2000) Human nerve growth factor protects common marmosets against autoimmune encephalomyelitis by switching the balance of T helper cell type 1 and 2 cytokines within the central nervous system. J Exp Med 191:1799–1806PubMedCentralPubMedGoogle Scholar
  105. Wang LJ, Lu YY, Muramatsu S, Ikeguchi K, Fujimoto K, Okada T, Mizukami H, Matsushita T, Hanazono Y, Kume A, Nagatsu T, Ozawa K, Nakano I (2002) Neuroprotective effects of glial cell line-derived neurotrophic factor mediated by an adeno-associated virus vector in a transgenic animal model of amyotrophic lateral sclerosis. J Neurosci 22:6920–6928PubMedGoogle Scholar
  106. Wang Q, Nan Tang X, Yenari MA (2007) The inflammatory response in stroke. J Neuroimmunol 184:53–68PubMedCentralPubMedGoogle Scholar
  107. Weber MS, Starck M, Wagenpfeil S, Meinl E, Hohlfeld R, Farina C (2004) Multiple sclerosis: glatiramer acetate inhibits monocyte reactivity in vitro and in vivo. Brain 127:1370–1378PubMedGoogle Scholar
  108. Weber MS, Prod’homme T, Youssef S, Dunn SE, Rundle CD, Lee L, Patarroyo JC, Stüve O, Sobel RA, Steinman L, Zamvil SS (2007) Type II monocytes modulate T-cell mediated central nervous system autoimmune disease. Nat Med 13:935–943PubMedGoogle Scholar
  109. Wong G, Goldshmit Y, Turnley AM (2004) Interferon-gamma but not TNF alpha promotes neuronal differentiation and neurite outgrowth of murine adult neuronal stem cells. Exp Neurol 187:171–177PubMedGoogle Scholar
  110. Xia Y, Hu HZ, Liu S, Ren J, Zafirov DH, Wood JD (1999) IL-1beta and IL-6 excite neurons and suppress nicotinic and noradrenergic neurotransmission in guinea pig enteric nervous system. J Clin Invest 103:1309–1316PubMedCentralPubMedGoogle Scholar
  111. Yang GY, Zhao YJ, Davidson BL, Betz AL (1997) Overexpression of interleukin-1 receptor antagonist in the mouse brain reduces ischemic brain injury. Brain Res 751:181–188PubMedGoogle Scholar
  112. Yoles E, Hauben E, Palgi O, Agranov E, Gothilf A, Cohen A, Kuchroo V, Cohen IR, Weiner H, Schwartz M (2001) Protective autoimmunity is a physiological response to CNS trauma. J Neurosci 21:3740–3748PubMedGoogle Scholar
  113. Zhang K, McQuibban GA, Silva C, Butler GS, Johnston JB, Holden J, Clark-Lewis I, Overall CM, Power C (2003) HIV-induced metalloproteinase processing of the chemokine stromal cell derived factor-1 causes neurodegeneration. Nat Neurosci 6:1064–1071PubMedGoogle Scholar
  114. Zhang RX, Liu B, Li A, Wang L, Ren K, Qiao JT, Berman BM, Lao L (2008) Interleukin 1beta facilitates bone cancer pain in rats by enhancing NMDA receptor NR-1 subunit phosphorylation. Neuroscience 154:1533–1538PubMedCentralPubMedGoogle Scholar
  115. Zhu Y, Yu T, Zhang XC, Nagasawa T, Wu JY, Rao Y. (2002) Role of the chemokine SDF-1 as the meningeal attractent for embryonic cerebellar neurons. Nat Neurosci 5:719–720PubMedCentralPubMedGoogle Scholar
  116. Ziemssen T, Kümpfel T, Klinkert WE, Neuhaus O, Hohlfeld R (2002) Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy. Brain 125:2381–2391PubMedGoogle Scholar
  117. Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, Cohen H, Kipnis J, Schwartz M (2006) Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci 9:268–275PubMedGoogle Scholar

Copyright information

© Springer Berlin Heidelberg 2009

Authors and Affiliations

  • Martin Kerschensteiner
    • 1
  • Edgar Meinl
    • 1
  • Reinhard Hohlfeld
    • 1
  1. 1.Institute of Clinical NeuroimmunologyLudwig-Maximilians University MunichMunichGermany

Personalised recommendations