A multiple sclerosis-associated variant of CBLB Links genetic risk with type I IFN function

Journal of Immunology

Volumn 193, Issue 9, 2014, Pages 4439-4447

  Stürner, Klarissa Hanja ^a   Borgmeyer, Uwe ^a   Schulze, Christian ^a   Pless, Ole ^b   Martin, Roland ^a,c  

^a UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^b FRAUNHOFER INSTITUTE FOR MOLECULAR BIOLOGY AND APPLIED ECOLOGY IME   (Germany)

^c UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

BETA INTERFERON; CCAAT ENHANCER BINDING PROTEIN BETA; INTERFERON; CBL PROTEIN; CBLB PROTEIN, HUMAN; PROTEIN BINDING; SIGNAL TRANSDUCING ADAPTOR PROTEIN;

ARTICLE; CASITAS B LINEAGE LYMPHOMA PROTO ONCOGENE B GENE; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; EXPANDED DISABILITY STATUS SCALE; FEMALE; GENE EXPRESSION; GENE LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; HOMOZYGOTE; HUMAN; HUMAN CELL; LYMPHOCYTE PROLIFERATION; MAJOR CLINICAL STUDY; MALE; MULTIPLE SCLEROSIS; NUCLEOTIDE SEQUENCE; PROTO ONCOGENE; RELAPSE; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSCRIPTION REGULATION; ALLELE; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION; GENETICS; GENOTYPE; IMMUNOLOGY; METABOLISM; PHENOTYPE; TREATMENT OUTCOME;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ALLELES; CCAAT-ENHANCER-BINDING PROTEIN-BETA; CD4-POSITIVE T-LYMPHOCYTES; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; GENOTYPE; HUMANS; INTERFERON TYPE I; MULTIPLE SCLEROSIS; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS C-CBL; TREATMENT OUTCOME;

EID: 84908142768     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1303077     Document Type: Article

References (51)

1. Ramagopalan, S. V., R. Dobson, U. C. Meier, and G. Giovannoni. 2010. Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol. 9: 727-739.
2. Sospedra, M., and R. Martin. 2005. Immunology of multiple sclerosis. Annu. Rev. Immunol. 23: 683-747.
3. International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, S. Sawcer, G. Hellenthal, M. Pirinen, C. C. Spencer, N. A. Patsopoulos, L. Moutsianas, A. Dilthey, Z. Su, C. Freeman, S. E. Hunt, et al. 2011. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476: 214-219.
4. International Multiple Sclerosis Genetics Consortium, A. H. Beecham, N. A. Patsopoulos, D. K. Xifara, M. F. Davis, A. Kemppinen, C. Cotsapas, T. S. Shah, C. Spencer, D. Booth, A. Goris, et al. 2013. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat. Genet. 45: 1353-1360.
5. Gregory, A. P., C. A. Dendrou, K. E. Attfield, A. Haghikia, D. K. Xifara, F. Butter, G. Poschmann, G. Kaur, L. Lambert, O. A. Leach, et al. 2012. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature 488: 508-511.
6. Gregory, S. G., S. Schmidt, P. Seth, J. R. Oksenberg, J. Hart, A. Prokop, S. J. Caillier, M. Ban, A. Goris, L. F. Barcellos, et al.; Multiple Sclerosis Genetics Group. 2007. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat. Genet. 39: 1083-1091.
7. Kreft, K. L., E. Verbraak, A. F. Wierenga-Wolf, M. van Meurs, B. A. Oostra, J. D. Laman, and R. Q. Hintzen. 2012. Decreased systemic IL-7 and soluble IL-7Rα in multiple sclerosis patients. Genes Immun. 13: 587-592.
8. International Multiple Sclerosis Genetics Consortium, D. A. Hafler, A. Compston, S. Sawcer, E. S. Lander, M. J. Daly, P. L. De Jager, P. I. de Bakker, S. B. Gabriel, D. B. Mirel, A. J. Ivinson, et al. 2007. Risk alleles for multiple sclerosis identified by a genomewide study. N. Engl. J. Med. 357: 851-862.
9. Sanna, S., M. Pitzalis, M. Zoledziewska, I. Zara, C. Sidore, R. Murru, M. B. Whalen, F. Busonero, A. Maschio, G. Costa, et al. 2010. Variants within the immunoregulatory CBLB gene are associated with multiple sclerosis. Nat. Genet. 42: 495-497.
10. Bachmaier, K., C. Krawczyk, I. Kozieradzki, Y. Y. Kong, T. Sasaki, A. Oliveirados-Santos, S. Mariathasan, D. Bouchard, A. Wakeham, A. Itie, et al. 2000. Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b. Nature 403: 211-216.
11. Chiang, Y. J., H. K. Kole, K. Brown, M. Naramura, S. Fukuhara, R. J. Hu, I. K. Jang, J. S. Gutkind, E. Shevach, and H. Gu. 2000. Cbl-b regulates the CD28 dependence of T-cell activation. Nature 403: 216-220.
12. Dubey, C., M. Croft, and S. L. Swain. 1996. Naive and effector CD4 T cells differ in their requirements for T cell receptor versus costimulatory signals. J. Immunol. 157: 3280-3289.
13. Yokoi, N., K. Komeda, H. Y. Wang, H. Yano, K. Kitada, Y. Saitoh, Y. Seino, K. Yasuda, T. Serikawa, and S. Seino. 2002. Cblb is a major susceptibility gene for rat type 1 diabetes mellitus. Nat. Genet. 31: 391-394.
14. Hoyne, G. F., E. Flening, M. Yabas, C. Teh, J. A. Altin, K. Randall, C. B. Thien, W. Y. Langdon, and C. C. Goodnow. 2011. Visualizing the role of Cbl-b in control of islet-reactive CD4 T cells and susceptibility to type 1 diabetes. J. Immunol. 186: 2024-2032.
15. Paolino, M., and J. M. Penninger. 2010. Cbl-b in T-cell activation. Semin. Immunopathol. 32: 137-148.
16. Zhou, W. B., R. Wang, Y. N. Deng, X. B. Ji, G. X. Huang, and Y. Z. Xu. 2008. Study of Cbl-b dynamics in peripheral blood lymphocytes isolated from patients with multiple sclerosis. Neurosci. Lett. 440: 336-339.
17. Mohme, M., C. Hotz, S. Stevanovic, T. Binder, J. H. Lee, M. Okoniewski, T. Eiermann, M. Sospedra, H. G. Rammensee, and R. Martin. 2013. HLA-DR15-derived self-peptides are involved in increased autologous T cell proliferation in multiple sclerosis. Brain 136: 1783-1798.
18. Río, J., C. Nos, M. Tintoré, N. Téllez, I. Galán, R. Pelayo, M. Comabella, and X. Montalban. 2006. Defining the response to interferon-beta in relapsing-remitting multiple sclerosis patients. Ann. Neurol. 59: 344-352.
19. 1000 Genomes Project Consortium, G. R. Abecasis, A. Auton, L. D. Brooks, M. A. DePristo, R. M. Durbin, R. E. Handsaker, H. M. Kang, G. T. Marth, and G. A. McVean. 2012. An integrated map of genetic variation from 1,092 human genomes. Nature 491: 56-65.
20. Kel, A. E., E. Gössling, I. Reuter, E. Cheremushkin, O. V. Kel-Margoulis, and E. Wingender. 2003. MATCH: A tool for searching transcription factor binding sites in DNA sequences. Nucleic Acids Res. 31: 3576-3579.
21. Pless, O., E. Kowenz-Leutz, M. Knoblich, J. Lausen, M. Beyermann, M. J. Walsh, and A. Leutz. 2008. G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta. J. Biol. Chem. 283: 26357-26363.
22. Chomczynski, P., and N. Sacchi. 2006. The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on. Nat. Protoc. 1: 581-585.
23. D'Netto, M. J., H. Ward, K. M. Morrison, S. V. Ramagopalan, D. A. Dyment, G. C. DeLuca, L. Handunnetthi, A. D. Sadovnick, and G. C. Ebers. 2009. Risk alleles for multiple sclerosis in multiplex families. Neurology 72: 1984-1988.
24. Ramji, D. P., and P. Foka. 2002. CCAAT/enhancer-binding proteins: structure, function and regulation. Biochem. J. 365: 561-575.
25. Lock, C., G. Hermans, R. Pedotti, A. Brendolan, E. Schadt, H. Garren, A. Langer-Gould, S. Strober, B. Cannella, J. Allard, et al. 2002. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. 8: 500-508.
26. Bristol, J. A., A. R. Robinson, E. A. Barlow, and S. C. Kenney. 2010. The Epstein-Barr virus BZLF1 protein inhibits tumor necrosis factor receptor 1 expression through effects on cellular C/EBP proteins. J. Virol. 84: 12362-12374.
27. Ravimohan, S., L. Gama, S. A. Barber, and J. E. Clements. 2010. Regulation of SIV mac 239 basal long terminal repeat activity and viral replication in macrophages: functional roles of two CCAAT/enhancer-binding protein beta sites in activation and interferon beta-mediated suppression. J. Biol. Chem. 285: 2258-2273.
28. Comabella, M., J. D. Lunemann, J. Rio, A. Sanchez, C. Lopez, E. Julia, M. Fernandez, L. Nonell, M. Camina-Tato, F. Deisenhammer, E. Caballero, M. T. Tortola, M. Prinz, X. Montalban, and R. Martin. 2009. A type I interferon signature in monocytes is associated with poor response to interferon-beta in multiple sclerosis. Brain 132: 3353-3365.
29. Rudick, R. A., M. R. Rani, Y. Xu, J. C. Lee, J. Na, J. Shrock, A. Josyula, E. Fisher, and R. M. Ransohoff. 2011. Excessive biologic response to IFNβ is associated with poor treatment response in patients with multiple sclerosis. PLoS ONE 6: e19262.
30. Huber, J. P., and J. D. Farrar. 2011. Regulation of effector and memory T-cell functions by type I interferon. Immunology 132: 466-474.
31. Gómez-Martín, D., M. Ibarra-Sánchez, J. Romo-Tena, J. Cruz-Ruíz, J. Esparza-López, M. Galindo-Campos, M. Díaz-Zamudio, and J. Alcocer-Varela. 2013. Casitas B lineage lymphoma b is a key regulator of peripheral tolerance in systemic lupus erythematosus. Arthritis Rheum. 65: 1032-1042.
32. Harada, Y., Y. Harada, C. Elly, G. Ying, J. H. Paik, R. A. DePinho, and Y. C. Liu. 2010. Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells. J. Exp. Med. 207: 1381-1391.
33. Qiao, G., Y. Zhao, Z. Li, P. Q. Tang, W. Y. Langdon, T. Yang, and J. Zhang. 2013. T cell activation threshold regulated by E3 ubiquitin ligase Cbl-b determines fate of inducible regulatory T cells. J. Immunol. 191: 632-639.
34. Viglietta, V., C. Baecher-Allan, H. L. Weiner, and D. A. Hafler. 2004. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med. 199: 971-979.
35. Simón-Sánchez, J., and A. Singleton. 2008. Genome-wide association studies in neurological disorders. Lancet Neurol. 7: 1067-1072.
36. Baranzini, S. E., N. W. Galwey, J. Wang, P. Khankhanian, R. Lindberg, D. Pelletier, W. Wu, B. M. Uitdehaag, L. Kappos, C. H. Polman, et al.; GeneMSA Consortium. 2009. Pathway and network-based analysis of genome-wide association studies in multiple sclerosis. Hum. Mol. Genet. 18: 2078-2090.
37. McCarthy, M. I., G. R. Abecasis, L. R. Cardon, D. B. Goldstein, J. Little, J. P. Ioannidis, and J. N. Hirschhorn. 2008. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat. Rev. Genet. 9: 356-369.
38. Wang, K., S. P. Dickson, C. A. Stolle, I. D. Krantz, D. B. Goldstein, and H. Hakonarson. 2010. Interpretation of association signals and identification of causal variants from genome-wide association studies. Am. J. Hum. Genet. 86: 730-742.
39. Edwards, S. L., J. Beesley, J. D. French, and A. M. Dunning. 2013. Beyond GWASs: illuminating the dark road from association to function. Am. J. Hum. Genet. 93: 779-797.
40. Kondo, T., I. Cortese, S. Markovic-Plese, K. P. Wandinger, C. Carter, M. Brown, S. Leitman, and R. Martin. 2001. Dendritic cells signal T cells in the absence of exogenous antigen. Nat. Immunol. 2: 932-938.
41. Sibley, W. A., C. R. Bamford, and K. Clark. 1985. Clinical viral infections and multiple sclerosis. Lancet 1: 1313-1315.
42. van Baarsen, L. G., T. C. van der Pouw Kraan, J. J. Kragt, J. M. Baggen, F. Rustenburg, T. Hooper, J. F. Meilof, M. J. Fero, C. D. Dijkstra, C. H. Polman, and C. L. Verweij. 2006. A subtype of multiple sclerosis defined by an activated immune defense program. Genes Immun. 7: 522-531.
43. Welm, A. L., S. L. Mackey, L. T. Timchenko, G. J. Darlington, and N. A. Timchenko. 2000. Translational induction of liver-enriched transcriptional inhibitory protein during acute phase response leads to repression of CCAAT/enhancer binding protein alpha mRNA. J. Biol. Chem. 275: 27406-27413.
44. Kowenz-Leutz, E., and A. Leutz. 1999. A C/EBP beta isoform recruits the SWI/SNF complex to activate myeloid genes. Mol. Cell 4: 735-743.
45. Ki, S. H., I. J. Cho, D. W. Choi, and S. G. Kim. 2005. Glucocorticoid receptor (GR)-associated SMRT binding to C/EBPbeta TAD and Nrf2 Neh4/5: role of SMRT recruited to GR in GSTA2 gene repression. Mol. Cell. Biol. 25: 4150-4165.
46. Raghav, S. K., S. M. Waszak, I. Krier, C. Gubelmann, A. Isakova, T. S. Mikkelsen, and B. Deplancke. 2012. Integrative genomics identifies the corepressor SMRT as a gatekeeper of adipogenesis through the transcription factors C/EBPb and KAISO. Mol. Cell 46: 335-350.
47. Kowenz-Leutz, E., O. Pless, G. Dittmar, M. Knoblich, and A. Leutz. 2010. Crosstalk between C/EBPbeta phosphorylation, arginine methylation, and SWI/SNF/Mediator implies an indexing transcription factor code. EMBO J. 29: 1105-1115.
48. Parkin, S. E., M. Baer, T. D. Copeland, R. C. Schwartz, and P. F. Johnson. 2002. Regulation of CCAAT/enhancer-binding protein (C/EBP) activator proteins by heterodimerization with C/EBPgamma (Ig/EBP). J. Biol. Chem. 277: 23563-23572.
49. Comabella, M., D. W. Craig, C. Morcillo-Suárez, J. Río, A. Navarro, M. Fernández, R. Martin, and X. Montalban. 2009. Genome-wide scan of 500,000 single-nucleotide polymorphisms among responders and nonresponders to interferon beta therapy in multiple sclerosis. Arch. Neurol. 66: 972-978.
50. Akira, S., H. Isshiki, T. Sugita, O. Tanabe, S. Kinoshita, Y. Nishio, T. Nakajima, T. Hirano, and T. Kishimoto. 1990. A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J. 9: 1897-1906.
51. Sellebjerg, F., M. Krakauer, M. Khademi, T. Olsson, and P. S. Sørensen. 2012. FOXP3, CBLB and ITCH gene expression and cytotoxic T lymphocyte antigen 4 expression on CD4(+) CD25(high) T cells in multiple sclerosis. Clin. Exp. Immunol. 170: 149-155.