High-dimensional single-cell analysis reveals the immune signature of narcolepsy

Journal of Experimental Medicine

Volumn 213, Issue 12, 2016, Pages 2621-2633

  Hartmann, Felix J ^b   Bernard Valnet, Raphaël ^a   Quériault, Clémence ^a   Mrdjen, Dunja ^b   Weber, Lukas M ^b   Galli, Edoardo ^b   Krieg, Carsten ^b   Robinson, Mark D ^b   Nguyen, Xuan Hung ^a   Dauvilliers, Yves ^c   Liblau, Roland S ^a   Becher, Burkhard ^b  

^a CNRS   (France)

^b UNIVERSITY OF ZURICH   (Switzerland)

^c INSERM   (France)

Author keywords

[No Author keywords available]

Indexed keywords

HLA DQB1 ANTIGEN; TUMOR NECROSIS FACTOR; CYTOKINE; INFLUENZA VACCINE;

ADOLESCENT; ADULT; ARTICLE; AUTOIMMUNITY; B LYMPHOCYTE; BLOOD SAMPLING; CATAPLEXY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CHILD; CLINICAL ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; DAYTIME SOMNOLENCE; DISEASE ASSOCIATION; FEMALE; HLA TYPING; HUMAN; HUMAN CELL; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; INTERNATIONAL CLASSIFICATION OF SLEEP DISORDERS; MALE; MEMORY CELL; NARCOLEPSY; PERIPHERAL BLOOD MONONUCLEAR CELL; PHENOTYPE; PRIORITY JOURNAL; SINGLE CELL ANALYSIS; TH1 CELL; TH2 CELL; CASE CONTROL STUDY; CELL PROLIFERATION; FLOW CYTOMETRY; HELPER CELL; IMMUNITY; IMMUNOLOGY; IMMUNOPHENOTYPING; LYMPHOCYTE ACTIVATION; METABOLISM; MIDDLE AGED; PRESCHOOL CHILD; PROCEDURES; VACCINATION;

ADOLESCENT; ADULT; B-LYMPHOCYTES; CASE-CONTROL STUDIES; CD8-POSITIVE T-LYMPHOCYTES; CELL PROLIFERATION; CHILD; CHILD, PRESCHOOL; CYTOKINES; FEMALE; FLOW CYTOMETRY; HUMANS; IMMUNITY; IMMUNOPHENOTYPING; INFLUENZA VACCINES; LYMPHOCYTE ACTIVATION; MALE; MIDDLE AGED; NARCOLEPSY; PHENOTYPE; SINGLE-CELL ANALYSIS; T-LYMPHOCYTES, HELPER-INDUCER; TUMOR NECROSIS FACTOR-ALPHA; VACCINATION;

EID: 84999792441     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20160897     Document Type: Article

References (60)

1. Ackermann, K., VL. Revell, O. Lao, E. J. Rombouts, DJ. Skene, and M. Kayser. 2012. Diurnal rhythms in blood cell populations and the effect of acute sleep deprivation in healthy young men. Sleep. 35:933-940. http://dx.doi.org/10.5665/sleep. 1954
2. Ahmed, S. S., W. Volkmuth, J. Duca, L. Corti, M. Pallaoro, A. Pezzicoli, A. Karle, F. Rigat, R. Rappuoli, V Narasimhan, et al. 2015. Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. Sci. Transl. Med. 7:294ra105. http://dx.doi.org/10.1126/scitranslmed. aab2354
3. Aho, V., H. M. Ollila, V. Rantanen, E. Kronholm, I. Surakka, W. M. A. van Leeuwen, M. Lehto, S. Matikainen, S. Ripatti, M. Harma, et al. 2013. Partial sleep restriction activates immune response-related gene expression pathways: experimental and epidemiological studies in humans. PLoS One. 8:e77184. http://dx.doi.org/10.1371/journal. pone. 0077184
4. American Academy of Sleep Disorders. 2014. International Classification of Sleep Disorders. Third edition. M. Sateia, editor. American Academy of Sleep Medicine, Darien, IL. 383 pp.
5. Amir, A. D., K. L. Davis, M. D. Tadmor, E. F Simonds, J. H. Levine, S. C. Bendall, D. K. Shenfeld, S. Krishnaswamy, G. P. Nolan, and D. Pe'er. 2013. viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat. Biotechnol. 31:545-552. http://dx.doi.org/10.1038/nbt. 2594
6. Becher, B., and S. Pantelyushin. 2012. Hiding under the skin: Interleukin-17-producing yfi T cells go under the skin. Nat. Med. 18:1748-1750. http://dx.doi.org/10.1038/nm. 3016
7. Behbehani, G. K., N. Samusik, Z. B. Bjornson, WJ. Fantl, B. C. Medeiros, and G. P. Nolan. 2015. Mass Cytometric Functional Profiling of Acute Myeloid Leukemia Defines Cell-Cycle and Immunophenotypic Properties That Correlate with Known Responses to Therapy. Cancer Discov. 5:988-1003. http://dx.doi.org/10.1158/2159-8290. CD-15
8. Bendall, S. C., E. F. Simonds, P. Qiu, A. D. Amir, P. O. Krutzik, R. Finck, R. V. Bruggner, R. Melamed, A. Trejo, O. I. Ornatsky, et al. 2011. Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science.332:687-696. http://dx.doi.org/10.1126/science.1198704
9. Bendall, S. C., G. P. Nolan, M. Roederer, and P. K. Chattopadhyay. 2012. A deep profiler's guide to cytometry. Trends Immunol. 33:323-332. http://dx.doi.org/10.1016/j.it. 2012. 02. 010
10. Bergman, P., C. Adori, S. Vas, Y. Kai-Larsen, T. Sarkanen, A. Cederlund, B. Agerberth, I. Julkunen, B. Horvath, D. Kostyalik, et al. 2014. Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns. Proc. Natl. Acad. Sci. USA. 111:E3735-E3744. http://dx.doi.org/10.1073/pnas. 1412189111
11. Berhanu, D., F. Mortari, S. C. De Rosa, and M. Roederer. 2003. Optimized lymphocyte isolation methods for analysis of chemokine receptor expression. J. Immunol. Methods. 279:199-207. http://dx.doi.org/10.1016/S0022-1759(03)00186-8
12. Bernard-Valnet, R., L. Yshii, C. Queriault, X.-H. Nguyen, S. Arthaud, M. Rodrigues, A. Canivet, A.-L. Morel, A. Matthys, J. Bauer, et al. 2016. CD8 T cell-mediated killing of orexinergic neurons induces a narcolepsy-like phenotype in mice. Proc. Natl. Acad. Sci. USA. 113:10956-10961. http://dx.doi.org/10.1073/pnas. 1603325113
13. Carr, E. J., J. Dooley, J. E. Garcia-Perez, V Lagou, J. C. Lee, C. Wouters, I. Meyts, A. Goris, G. Boeckxstaens, M. A. Linterman, and A. Liston. 2016. The cellular composition of the human immune system is shaped by age and cohabitation. Nat. Immunol. 17:461-468. http://dx.doi.org/10.1038/ni. 3371
14. Cvetkovic-Lopes, V., L. Bayer, S. Dorsaz, S. Maret, S. Pradervand, Y. Dauvilliers, M. Lecendreux, G.-J. Lammers, C. E. H. M. Donjacour, R. A. Du Pasquier, et al. 2010. Elevated Tribbles homolog 2-specific antibody levels in narcolepsy patients. J. Clin. Invest. 120:713-719. http://dx.doi.org/10.1172/JCI41366
15. Dauvilliers, Y., I. Arnulf, and E. Mignot. 2007. Narcolepsy with cataplexy. Lancet. 369:499-511. http://dx.doi.org/10.1016/S0140-6736(07)60237-2
16. Dauvilliers, Y., I. Jaussent, M. Lecendreux, S. Scholz, S. Bayard, J. P. Cristol, H. Blain, and A.-M. Dupuy. 2014. Cerebrospinal fluid and serum cytokine profiles in narcolepsy with cataplexy: a case-control study. Brain Behav Immun. 37:260-266. http://dx.doi.org/10.10167j. bbi. 2013. 12. 019
17. Dendrou, C. A., L. Fugger, and M. A. Friese. 2015. Immunopathology of multiple sclerosis. Nat. Rev. Immunol. 15:545-558. http://dx.doi.org/10.1038/nri3871
18. Fienberg, H. G., E. F Simonds, WJ. Fantl, G. P. Nolan, and B. Bodenmiller. 2012. A platinum-based covalent viability reagent for single-cell mass cytometry. Cytometry A. 81:467-475. http://dx.doi.org/10.1002/cyto. a. 22067
19. Filiano, A. J., Y. Xu, N. J. Tustison, R. L. Marsh, W Baker, I. Smirnov, C. C. Overall, S. P. Gadani, S. D. Turner, Z. Weng, et al. 2016. Unexpected role of interferon-y in regulating neuronal connectivity and social behaviour. Nature. 535:425-429. http://dx.doi.org/10.1038/nature18626
20. Finck, R., E. F Simonds, A. Jager, S. Krishnaswamy, K. Sachs, W Fantl, D. Pe'er, G. P. Nolan, and S. C. Bendall. 2013. Normalization of mass cytometry data with bead standards. Cytometry A. 83:483-494. http://dx.doi.org/10.1002/cyto. a. 22271
21. Flach, A.-C., T. Litke, J. Strauss, M. Haberl, C. C. Gomez, M. Reindl, A. Saiz, H.-J. Fehling, J. Wienands, F Odoardi, et al. 2016. Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease. Proc. Natl. Acad. Sci. USA. 113:3323-3328. http://dx.doi.org/10.1073/pnas. 1519608113
22. Gaudilliere, B., G. K. Fragiadakis, R. V Bruggner, M. Nicolau, R. Finck, M. Tingle, J. Silva, E. A. Ganio, C. G. Yeh, WJ. Maloney, et al. 2014. Clinical recovery from surgery correlates with single-cell immune signatures. Sci. Transl. Med. 6:255ra131. http://dx.doi.org/10.1126/scitranslmed. 3009701
23. Gromping, U. 2006. Relative Importance for Linear Regression in R: The Package relaimpo. J. Stat. Softw 17:1-27. http://dx.doi.org/10.18637/jss. v017. i01
24. Han, F, J. Faraco X. S. Dong H. M. Ollila L. Lin J. Li P. An S. Wang K. W Jiang Z. C. Gao, et al. 2013. Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic. PLoS Genet. 9:e1003880. http://dx.doi.org/10.1371/journal. pgen. 1003880
25. Himmerich, H., PA. Beitinger S. Fulda, R. Wehrle, J. Linseisen, G. Wolfram, S. Himmerich, K. Gedrich, T. C. Wetter, and T. Pollmacher. 2006. Plasma levels of tumor necrosis factor alpha and soluble tumor necrosis factor receptors in patients with narcolepsy. Arch. Intern. Med. 166:1739-1743. http://dx.doi.org/10.1001/archinte. 166. 16. 1739
26. Hohjoh, H., T. Nakayama, J. Ohashi, T. Miyagawa, H. Tanaka, T. Akaza, Y. Honda, T. Juji, and K. Tokunaga. 1999. Significant association of a single nucleotide polymorphism in the tumor necrosis factor-alpha (TNF-alpha) gene promoter with human narcolepsy. Tissue Antigens. 54:138145. http://dx.doi.org/10.1034/j.1399-0039. 1999. 540204. x
27. Huang, J., X. Zeng, N. Sigal, PJ. Lund, L. F Su, H. Huang, Y. H. Chien, and M. M. Davis. 2016. Detection, phenotyping, and quantification of antigen-specific T cells using a peptide-MHC dodecamer. Proc. Natl. Acad. Sci. USA. 113:E1890-E1897. http://dx.doi.org/10.1073/pnas. 1602488113
28. Kim, M. S., J. Yan, W Wu, G. Zhang, Y. Zhang, and D. Cai. 2015. Rapid linkage of innate immunological signals to adaptive immunity by the brain-fat axis. Nat. Immunol. 16:525-533. http://dx.doi.org/10.1038/ni. 3133
29. Kornum, B. R., F. Pizza, S. Knudsen, G. Plazzi, P. Jennum, and E. Mignot. 2015. Cerebrospinal fluid cytokine levels in type 1 narcolepsy patients very close to onset. Brain Behav Immun. 49:54-58. http://dx.doi.org/10.1016/j.bbi. 2015. 03. 004
30. Krumbholz, M., T. Derfuss, R. Hohlfeld, and E. Meinl. 2012. B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat. R ev. Neurol. 8:613-623. http://dx.doi.org/10.1038/nrneurol. 2012. 203
31. Lasselin, J., J. U. Rehman, T. Akerstedt, M. Lekander, and J. Axelsson. 2015. Effect of long-term sleep restriction and subsequent recovery sleep on the diurnal rhythms of white blood cell subpopulations. Brain Behav. Immun. 47:93-99. http://dx.doi.org/10.1016/j.bbi. 2014. 10. 004
32. Levine, J. H., E. F Simonds, S. C. Bendall, K. L. Davis, A. D. Amir, M. D. Tadmor, O. Litvin, H. G. Fienberg, A. Jager, E. R. Zunder, et al. 2015. Data-Driven Phenotypic Dissection of AML Reveals Progenitor-like Cells that Correlate with Prognosis. Cell. 162:184-197. http://dx.doi.org/10.1016/j.cell.2015. 05. 047
33. Liblau, R. S., A. Vassalli, A. Seifinejad, and M. Tafti. 2015. Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy. Lancet Neurol. 14:318-328. http://dx.doi.org/10.1016/S1474-4422(14)70218-2
34. Louveau, A., I. Smirnov, T. J. Keyes, J. D. Eccles, S. J. Rouhani, J. D. Peske, N. C. Derecki, D. Castle, J. W Mandell, K. S. Lee, et al. 2015. Structural and functional features of central nervous system lymphatic vessels. Nature. 523:337-341. http://dx.doi.org/10.1038/nature14432
35. Mair, F, F. J. Hartmann, D. Mrdjen, V Tosevski, C. Krieg, and B. Becher. 2016. The end of gating. An introduction to automated analysis of high dimensional cytometry data. Eur. J. Immunol. 46:34-43. http://dx.doi.org/10.1002/eji. 201545774
36. McDonald, J. 2014. Handbook of Biological Statistics. Third edition. Sparky House Publishing, Baltimore, Maryland.
37. McKinney, E. F, J. C. Lee D. R. W Jayne PA. Lyons and K. G. C. Smith. 2015. T-cell exhaustion co-stimulation and clinical outcome in autoimmunity and infection. Nature. 523:612-616. http://dx.doi.org/10.1038/
38. Mei, H. E., M. D. Leipold A. R. Schulz C. Chester and H. T. Maecker. 2015. Barcoding of live human peripheral blood mononuclear cells for multiplexed mass cytometry. J. Immunol. 194:2022-2031. http://dx.doi.org/10.4049/jimmunol. 1402661
39. Mignot, E., R. Hayduk, J. Black, FC. Grumet, and C. Guilleminault. 1997. HLA DQB1, 0602 is associated with cataplexy in 509 narcoleptic patients. Sleep. 20:1012-1020.
40. Nguyen, X.-H., A. Saoudi, and R. S. Liblau. 2016. Vaccine-associated inflammatory diseases of the central nervous system: from signals to causation. Curr. Opin. Neurol. 29:362-371. http://dx.doi.org/10.1097/WCO. 0000000000000318
41. Noble, W. S. 2009. How does multiple testing correction work. Nat. Biotechnol. 27:1135-1137. http://dx.doi.org/10.1038/nbt1209-1135
42. Ollila, H. M., J.-M. Ravel F. Han J. Faraco L. Lin X. Zheng G. Plazzi Y. Dauvilliers F Pizza S.-C. Hong et al. 2015. HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy. Am. J. Hum. Genet. 96:136-146. http://dx.doi.org/10.1016/j.ajhg. 2014. 12. 010
43. Pepper, M., J. L. Linehan A. J. Pagan, T. Zell, T. Dileepan, PP Cleary, and M. K. Jenkins. 2010. Different routes of bacterial infection induce long-lived Th1 memory cells and short-lived TH17 cells. Nat. Immunol. 11:83-89. http://dx.doi.org/10.1038/ni. 1826
44. Perera, G. K., P Di Meglio, and F. O. Nestle. 2012. Psoriasis. Annu. Rev. Pathol. 7:385-422. http://dx.doi.org/10.1146/annurev-pathol-011811-132448
45. Pizza, F, H. Peltola, T. Sarkanen, K. K. Moghadam, G. Plazzi, and M. Partinen. 2014. Childhood narcolepsy with cataplexy: comparison between post-H1N1 vaccination and sporadic cases. Sleep Med. 15:262-265. http://dx.doi.org/10.1016/j.sleep. 2013. 09. 021
46. Saariaho, A.-H., A. Vuorela, T. L. Freitag, F. Pizza, G. Plazzi, M. Partinen, O. Vaarala, and S. Meri. 2015. Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after Pandemrix vaccination against 2009 pandemic H1N1 type influenza virus. J. Autoimmun. 63:68-75. http://dx.doi.org/10.1016/j.jaut. 2015. 07. 006
47. Scammell, T. E. 2015. Narcolepsy. N. Engl. J. Med. 373:2654-2662. http://dx.doi.org/10.1056/NEJMra1500587
48. Scheiermann, C., Y Kunisaki and PS. Frenette. 2013. Circadian control of the immune system. Nat. Rev Immunol. 13:190-198. http://dx.doi.org/10.1038/nri3386
49. Spitzer, M. H., P. F. Gherardini G. K. Fragiadakis N. Bhattacharya R. T. Yuan A. N. Hotson R. Finck Y Carmi E. R. Zunder WJ. Fantl et al. 2015. IMMUNOLOGY. An interactive reference framework for modeling a dynamic immune system. Science.349:1259425. http://dx.doi.org/10.1126/science.1259425
50. Tafti, M., H. Hor, Y Dauvilliers, G. J. Lammers, S. Overeem, G. Mayer, S. Javidi, A. Iranzo, J. Santamaria, R. Peraita-Adrados, et al. 2014. DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe. Sleep. 37:19-25. http://dx.doi.org/10.5665/sleep. 3300
51. Tafti, M., G. J. Lammers, Y Dauvilliers, S. Overeem, G. Mayer, J. Nowak, C. Pfister, V Dubois, J.-F. Eliaou, H.-P Eberhard, et al. 2016. Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity. Sleep. 39:581-587. http://dx.doi.org/10.5665/sleep. 5532
52. Tanaka, S., M. Honda, H. Toyoda, and T. Kodama. 2014. Increased plasma IL-6, IL-8, TNF-alpha, and G-CSF in Japanese narcolepsy. Hum. Immunol. 75:940-944. http://dx.doi.org/10.1016/j.humimm. 2014. 06. 023
53. Van Der Maaten, L., and G. Hinton. 2008. Visualizing Data using t-SNE. J. Mach. Learn. Res. 9:2579-2605. http://dx.doi.org/10.1007/s10479-011-0841-3
54. Van Gassen, S., B. Callebaut, M. J. Van Helden, B. N. Lambrecht, P Demeester, T. Dhaene, andY Saeys. 2015. FlowSOM: Using self-organizing maps for visualization and interpretation of cytometry data. Cytometry A. 87:636645. http://dx.doi.org/10.1002/cyto. a. 22625
55. Vgontzas, A. N., D. A. Papanicolaou E. O. Bixler A. Kales K. Tyson and G. P Chrousos. 1997. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin. Endocrinol. Metab. 82:1313-1316. http://dx.doi.org/10.1210/jcem. 82. 5. 3950
56. Waisman, A., R. S. Liblau, and B. Becher. 2015. Innate and adaptive immune responses in the CNS. Lancet Neurol. 14:945-955. http://dx.doi.org/10.1016/S1474-4422 (15)00141-6
57. Wolowczuk, I., C. Verwaerde, O. Viltart, A. Delanoye, M. Delacre, B. Pot, and C. Grangette. 2008. Feeding our immune system: impact on metabolism. Clin. Dev. Immunol. 2008:639803. http://dx.doi.org/10.1155/2008/639803
58. Yshii, L., C. Gebauer, R. Bernard-Valnet, and R. Liblau. 2015. Neurons and T cells: Understanding this interaction for inflammatory neurological diseases. Eur. J. Immunol. 45:2712-2720. http://dx.doi.org/10.1002/eji. 201545759
59. Yu, W, N. Jiang, P. J. R. Ebert, B. A. Kidd, S. Muller, P. J. Lund, J. Juang, K. Adachi, T. Tse, M. E. Birnbaum, et al. 2015. Clonal deletion prunes but does not eliminate self-specific ap CD8(+) T lymphocytes. Immunity 42:929-941. http://dx.doi.org/10.1016/j.immuni. 2015. 05. 001
60. Zunder, E. R., R. Finck, G. K. Behbehani, A. D. Amir, S. Krishnaswamy, VD. Gonzalez, C. G. Lorang, Z. Bjornson, M. H. Spitzer, B. Bodenmiller, et al. 2015. Palladium-based mass tag cell barcoding with a doublet-filtering scheme and single-cell deconvolution algorithm. Nat. Protoc. 10:316333. http://dx.doi.org/10.1038/nprot. 2015. 020