Sphingosine 1-phosphate receptor modulation suppresses pathogenic astrocyte activation and chronic progressive CNS inflammation

Proceedings of the National Academy of Sciences of the United States of America

Volumn 114, Issue 8, 2017, Pages 2012-2017

  Rothhammer, Veit ^a   Kenison, Jessica E ^a   Tjon, Emily ^a   Takenaka, Maisa C ^a   De Lima, Kalil Alves ^a   Borucki, Davis M ^a   Chao, Chun Cheih ^a   Wilz, Annabel ^a   Blain, Manon ^b   Healy, Luke ^b   Antel, Jack ^b   Quintana, Francisco J ^a,c  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b MCGILL UNIVERSITY   (Canada)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

Astrocytes; Eae; Multiple sclerosis; Secondary progression; Sphingolipid metabolism

Indexed keywords

FINGOLIMOD; FREUND ADJUVANT; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GAMMA INTERFERON RECEPTOR 1; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INDUCIBLE NITRIC OXIDE SYNTHASE; INFLAMMASOME; INTERLEUKIN 10; INTERLEUKIN 16; INTERLEUKIN 1BETA; INTERLEUKIN 23P19; INTERLEUKIN 6; LACTATE DEHYDROGENASE; MACROPHAGE INFLAMMATORY PROTEIN 3ALPHA; MONOCYTE CHEMOTACTIC PROTEIN 1; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; PERTUSSIS TOXIN; SPHINGOSINE 1 PHOSPHATE RECEPTOR; TRANSCRIPTION FACTOR RELA; TUMOR NECROSIS FACTOR; IMMUNOSUPPRESSIVE AGENT; S1PR1 PROTEIN, HUMAN; S1PR1 PROTEIN, MOUSE; SPHINGOSINE; TRANSCRIPTOME;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN PRESENTATION; ARTICLE; ASSAY; ASTROCYTE; ASTROCYTE CULTURE; CELL ACTIVATION; CELL INFILTRATION; CELL MIGRATION; CENTRAL NERVOUS SYSTEM; COCULTURE; CONTROLLED STUDY; DISEASE COURSE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FEMALE; GENE CLUSTER; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNIZATION; IN VITRO STUDY; IN VITRO TRANSWELL MIGRATION ASSAY; INNATE IMMUNITY; MICROGLIA; MONOCYTE; MOUSE; NERVE DEGENERATION; NEUROTOXICITY; NONHUMAN; POLARIZATION; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; UPREGULATION; ANIMAL; C57BL MOUSE; DISEASE EXACERBATION; DRUG EFFECTS; IMMUNOLOGY; METABOLISM; MULTIPLE SCLEROSIS; NONOBESE DIABETIC MOUSE; PATHOLOGY; PRIMARY CELL CULTURE; TUMOR CELL LINE;

ANIMALS; ASTROCYTES; CELL LINE, TUMOR; DISEASE PROGRESSION; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; FINGOLIMOD HYDROCHLORIDE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MICE; MICE, INBRED C57BL; MICE, INBRED NOD; MICROGLIA; MONOCYTES; MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE; PRIMARY CELL CULTURE; RECEPTORS, LYSOSPHINGOLIPID; SPHINGOSINE; TRANSCRIPTOME;

EID: 85013500971     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1615413114     Document Type: Article

References (71)

1. Mahad DH, Trapp BD, Lassmann H (2015) Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 14(2):183-193.
2. Rothhammer V, et al. (2016) Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med 22(6):586-597.
3. Mayo L, et al. (2014) Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nat Med 20(10):1147-1156.
4. Butovsky O, et al. (2014) Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat Neurosci 17(1):131-143.
5. Savarin C, et al. (2015) Astrocyte response to IFN-γ limits IL-6-mediated microglia activation and progressive autoimmune encephalomyelitis. J Neuroinflammation 12(1):79.
6. Lassmann H, van Horssen J, Mahad D (2012) Progressive multiple sclerosis: Pathology and pathogenesis. Nat Rev Neurol 8(11):647-656.
7. Tiper IV, East JE, Subrahmanyam PB, Webb TJ (2016) Sphingosine 1-phosphate signaling impacts lymphocyte migration, inflammation and infection. Pathog Dis 74(6): ftw063.
8. Garris CS, Blaho VA, Hla T, Han MH (2014) Sphingosine-1-phosphate receptor 1 signalling in T cells: Trafficking and beyond. Immunology 142(3):347-353.
9. Maceyka M, Spiegel S (2014) Sphingolipid metabolites in inflammatory disease. Nature 510(7503):58-67.
10. Brinkmann V (2009) FTY720 (fingolimod) in multiple sclerosis: Therapeutic effects in the immune and the central nervous system. Br J Pharmacol 158(5):1173-1182.
11. White C, Alshaker H, Cooper C, Winkler M, Pchejetski D (2016) The emerging role of FTY720 (fingolimod) in cancer treatment. Oncotarget 7(17):23106-23127.
12. Aoki M, Aoki H, Ramanathan R, Hait NC, Takabe K (2016) Sphingosine-1-phosphate signaling in immune cells and inflammation: Roles and therapeutic potential. Mediators Inflamm 2016:8606878.
13. Calabresi PA, et al. (2014) Safety and efficacy of fingolimod in patients with relapsingremitting multiple sclerosis (FREEDOMS II): A double-blind, randomised, placebocontrolled, phase 3 trial. Lancet Neurol 13(6):545-556.
14. Kappos L, et al.; FREEDOMS Study Group (2010) A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 362(5):387-401.
15. Hohlfeld R, Barkhof F, Polman C (2011) Future clinical challenges in multiple sclerosis: Relevance to sphingosine 1-phosphate receptor modulator therapy. Neurology 76(8, Suppl 3):S28-S37.
16. Hla T, Brinkmann V (2011) Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation. Neurology 76(8, suppl 3):S3-S8.
17. Mehling M, Johnson TA, Antel J, Kappos L, Bar-Or A (2011) Clinical immunology of the sphingosine 1-phosphate receptor modulator fingolimod (FTY720) in multiple sclerosis. Neurology 76(8, suppl 3):S20-S27.
18. Chun J, Hartung HP (2010) Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol 33(2):91-101.
19. Lee CW, Choi JW, Chun J (2010) Neurological S1P signaling as an emerging mechanism of action of oral FTY720 (fingolimod) in multiple sclerosis. Arch Pharm Res 33(10):1567-1574.
20. Brunkhorst R, Vutukuri R, Pfeilschifter W (2014) Fingolimod for the treatment of neurological diseases-state of play and future perspectives. Front Cell Neurosci 8:283.
21. Willis MA, Cohen JA (2013) Fingolimod therapy for multiple sclerosis. Semin Neurol 33(1):37-44.
22. Choi JW, et al. (2011) FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proc Natl Acad Sci USA 108(2):751-756.
23. Kim HJ, et al. (2011) Neurobiological effects of sphingosine 1-phosphate receptor modulation in the cuprizone model. FASEB J 25(5):1509-1518.
24. Colombo E, et al. (2014) Fingolimod may support neuroprotection via blockade of astrocyte nitric oxide. Ann Neurol 76(3):325-337.
25. Groves A, Kihara Y, Chun J (2013) Fingolimod: Direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy. J Neurol Sci 328(1-2):9-18.
26. Wu C, et al. (2013) Dual effects of daily FTY720 on human astrocytes in vitro: Relevance for neuroinflammation. J Neuroinflammation 10:41.
27. Miron VE, et al. (2010) Fingolimod (FTY720) enhances remyelination following demyelination of organotypic cerebellar slices. Am J Pathol 176(6):2682-2694.
28. Imeri F, et al. (2016) Sphingosine kinase 2 deficient mice exhibit reduced experimental autoimmune encephalomyelitis: Resistance to FTY720 but not ST-968 treatments. Neuropharmacology 105:341-350.
29. Foster CA, et al. (2009) FTY720 rescue therapy in the dark agouti rat model of experimental autoimmune encephalomyelitis: Expression of central nervous system genes and reversal of blood-brain-barrier damage. Brain Pathol 19(2):254-266.
30. Anthony DC, Sibson NR, Losey P, Meier DP, Leppert D (2014) Investigation of immune and CNS-mediated effects of fingolimod in the focal delayed-Type hypersensitivity multiple sclerosis model. Neuropharmacology 79:534-541.
31. di Nuzzo L, Orlando R, Nasca C, Nicoletti F (2014) Molecular pharmacodynamics of new oral drugs used in the treatment of multiple sclerosis. Drug Des Devel Ther 8: 555-568.
32. Simmons SB, Pierson ER, Lee SY, Goverman JM (2013) Modeling the heterogeneity of multiple sclerosis in animals. Trends Immunol 34(8):410-422.
33. Ignatius Arokia Doss PM, Roy AP, Wang A, Anderson AC, Rangachari M (2015) The non-obese diabetic mouse strain as a model to study CD8(+) T cell function in relapsing and progressive multiple sclerosis. Front Immunol 6:541.
34. Dang PT, Bui Q, D'Souza CS, Orian JM (2015) Modelling MS: Chronic-relapsing EAE in the NOD/Lt mouse strain. Curr Top Behav Neurosci 26:143-177.
35. Moreno M, et al. (2014) Conditional ablation of astroglial CCL2 suppresses CNS accumulation of M1 macrophages and preserves axons in mice with MOG peptide EAE. J Neurosci 34(24):8175-8185.
36. Ajami B, Bennett JL, Krieger C, McNagny KM, Rossi FM (2011) Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat Neurosci 14(9):1142-1149.
37. Mildner A, et al. (2009) CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain 132(pt 9):2487-2500.
38. Kim RY, et al. (2014) Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis. J Neuroimmunol 274(1-2):53-61.
39. Goldmann T, et al. (2013) A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation. Nat Neurosci 16(11):1618-1626.
40. Rothhammer V, Quintana FJ (2015) Control of autoimmune CNS inflammation by astrocytes. Semin Immunopathol 37(6):625-638.
41. Chen H, et al. (2015) Interleukin-33 is released in spinal cord and suppresses experimental autoimmune encephalomyelitis in mice. Neuroscience 308:157-168.
42. Jiang HR, et al. (2012) IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages. Eur J Immunol 42(7):1804-1814.
43. Huang DR, Wang J, Kivisakk P, Rollins BJ, Ransohoff RM (2001) Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J Exp Med 193(6):713-726.
44. Izikson L, Klein RS, Charo IF, Weiner HL, Luster AD (2000) Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J Exp Med 192(7):1075-1080.
45. Sofroniew MV (2015) Astrocyte barriers to neurotoxic inflammation. Nat Rev Neurosci 16(5):249-263.
46. Olabarria M, Putilina M, Riemer EC, Goldman JE (2015) Astrocyte pathology in Alexander disease causes a marked inflammatory environment. Acta Neuropathol 130(4):469-486.
47. Chung WS, Allen NJ, Eroglu C (2015) Astrocytes control synapse formation, function, and elimination. Cold Spring Harb Perspect Biol 7(9): A020370.
48. Lundgaard I, Osório MJ, Kress BT, Sanggaard S, Nedergaard M (2014) White matter astrocytes in health and disease. Neuroscience 276:161-173.
49. Lassmann H (2014) Mechanisms of white matter damage in multiple sclerosis. Glia 62(11):1816-1830.
50. Linne ML, Jalonen TO (2014) Astrocyte-neuron interactions: From experimental research- based models to translational medicine. Prog Mol Biol Transl Sci 123:191-217.
51. Brosnan CF, Raine CS (2013) The astrocyte in multiple sclerosis revisited. Glia 61(4): 453-465.
52. Ascherio A, Munger KL, Lünemann JD (2012) The initiation and prevention of multiple sclerosis. Nat Rev Neurol 8(11):602-612.
53. Lopes Pinheiro MA, et al. (2016) Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke. Biochim Biophys Acta 1862(3): 461-471.
54. Sheridan GK, Murphy KJ (2013) Neuronglia crosstalk in health and disease: Fractalkine and CX3CR1 take centre stage. Open Biol 3(12):130181.
55. Janssen S, et al. (2015) Effect of FTY720-phosphate on the expression of inflammation-Associated molecules in astrocytes in vitro. Mol Med Rep 12(4): 6171-6177.
56. Sheridan GK, Dev KK (2012) S1P1 receptor subtype inhibits demyelination and regulates chemokine release in cerebellar slice cultures. Glia 60(3):382-392.
57. Basso AS, et al. (2008) Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis. J Clin Invest 118(4):1532-1543.
58. Farez MF, et al. (2009) Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE. Nat Immunol 10(9):958-964.
59. Farez MF, Correale J (2016) Sphingosine 1-phosphate signaling in astrocytes: Implications for progressive multiple sclerosis. J Neurol Sci 361:60-65.
60. Healy LM, Antel JP (2016) Sphingosine-1-phosphate receptors in the central nervous and immune systems. Curr Drug Targets 17(16):1841-1850.
61. Nazari M, Keshavarz S, Rafati A, Namavar MR, Haghani M (2016) Fingolimod (FTY720) improves hippocampal synaptic plasticity and memory deficit in rats following focal cerebral ischemia. Brain Res Bull 124:95-102.
62. Tsai HC, Han MH (2016) Sphingosine-1-phosphate (S1P) and S1P signaling pathway: Therapeutic targets in autoimmunity and inflammation. Drugs 76(11):1067-1079.
63. Lublin F, et al.; INFORMS study investigators (2016) Oral fingolimod in primary progressive multiple sclerosis (INFORMS): A phase 3, randomised, double-blind, placebocontrolled trial. Lancet 387(10023):1075-1084.
64. O'Sullivan C, Schubart A, Mir AK, Dev KK (2016) The dual S1PR1/S1PR5 drug BAF312 (siponimod) attenuates demyelination in organotypic slice cultures. J Neuroinflammation 13:31.
65. Pan S, et al. (2013) Discovery of BAF312 (siponimod), a potent and selective S1P receptor modulator. ACS Med Chem Lett 4(3):333-337.
66. Briard E, Rudolph B, Desrayaud S, Krauser JA, Auberson YP (2015) MS565: A SPECT tracer for evaluating the brain penetration of BAF312 (siponimod). Chem Med Chem 10(6):1008-1018.
67. Kappos L, et al. (2016) Safety and efficacy of siponimod (BAF312) in patients with relapsing-remitting multiple sclerosis: Dose-blinded, randomized extension of the phase 2 bold study. JAMA Neurol 73(9):1089-1098.
68. Novartis Media Relations (2016) Novartis announces positive phase III results showing efficacy of BAF312 in patients with secondary progressive MS. Available at https://www.novartis.com/news/media-releases/novartis-Announces-positive-phase-iiiresults-showing-efficacy-baf312-patients. Accessed September 1, 2016.
69. Proia RL, Hla T (2015) Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest 125(4):1379-1387.
70. Asle-Rousta M, Kolahdooz Z, Oryan S, Ahmadiani A, Dargahi L (2013) FTY720 (fingolimod) attenuates beta-Amyloid peptide (Aβ42)-induced impairment of spatial learning and memory in rats. J Mol Neurosci 50(3):524-532.
71. Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9(7):671-675.