Eomesodermin-expressing T-helper cells are essential for chronic neuroinflammation

Nature Communications

Volumn 6, Issue , 2015, Pages

  Raveney, Ben J E ^a   Oki, Shinji ^a   Hohjoh, Hirohiko ^a   Nakamura, Masakazu ^a,b   Sato, Wakiro ^a,b   Murata, Miho ^b   Yamamura, Takashi ^a,b  

^a NATIONAL INSTITUTE OF NEUROSCIENCE   (Japan)

^b NATIONAL INSTITUTE OF MENTAL HEALTH   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

EOMESODERMIN; GRANZYME B; PROTEINASE ACTIVATED RECEPTOR 1; EOMES PROTEIN, HUMAN; EOMES PROTEIN, MOUSE; GRANZYME; NR4A2 PROTEIN, MOUSE; NUCLEAR RECEPTOR RELATED FACTOR 1; T BOX TRANSCRIPTION FACTOR;

BODY FLUID; CELLS AND CELL COMPONENTS; ENZYME ACTIVITY; EXPERIMENTAL STUDY; GENE EXPRESSION; IMMUNE SYSTEM; NERVOUS SYSTEM DISORDER; PROTEIN; RODENT;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOIMMUNITY; BLOOD; CD4+ T LYMPHOCYTE; CEREBROSPINAL FLUID; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOTOXIC T LYMPHOCYTE; EOMES GENE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GENE; GENE DELETION; GENE EXPRESSION; HUMAN; HUMAN CELL; MOUSE; MULTIPLE SCLEROSIS; NONHUMAN; PROTEIN EXPRESSION; TH17 CELL; ADULT; ANIMAL; FEMALE; GENETICS; HELPER CELL; IMMUNOLOGY; MALE; MIDDLE AGED; YOUNG ADULT;

MUS;

ADULT; ANIMALS; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; GRANZYMES; HUMANS; MALE; MICE; MIDDLE AGED; MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE; MULTIPLE SCLEROSIS, RELAPSING-REMITTING; NUCLEAR RECEPTOR SUBFAMILY 4, GROUP A, MEMBER 2; RECEPTOR, PAR-1; T-BOX DOMAIN PROTEINS; T-LYMPHOCYTES, HELPER-INDUCER; TH17 CELLS; YOUNG ADULT;

EID: 84943339273     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms9437     Document Type: Article

References (50)

1. The Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661-678 (2007).
2. Rioux, J. D. et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat. Genet. 39, 596-604 (2007).
3. International Multiple Sclerosis Genetics Consortium et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476, 214-219 (2011).
4. Doi, Y. et al. Orphan nuclear receptor NR4A2 expressed in T cells from multiple sclerosis mediates production of inflammatory cytokines. Proc. Natl Acad. Sci. USA 105, 8381-8386 (2008).
5. Satoh, J. et al. Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis. Neurobiol. Dis. 18, 537-550 (2005).
6. Raveney, B. J., Oki, S., Yamamura, T. Nuclear receptor NR4A2 orchestrates Th17 cell-mediated autoimmune inflammation via IL-21 signalling. PLoS ONE 8, e56595 (2013).
7. Law, S. W., Conneely, O. M., DeMayo, F. J., O'Malley, B. W. Identification of a new brain-specific transcription factor, NURR1. Mol. Endocrinol. 6, 2129-2135 (1992).
8. Perlmann, T., Wallen-Mackenzie, A. Nurr1, an orphan nuclear receptor with essential functions in developing dopamine cells. Cell Tissue Res. 318, 45-52 (2004).
9. Le, W. D. et al. Mutations in NR4A2 associated with familial Parkinson disease. Nat. Genet. 33, 85-89 (2003).
10. Sekiya, T. et al. Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis. Nat. Immunol. 14, 230-237 (2013).
11. Intlekofer, A. M. et al. Effector and memory CD8\+ T cell fate coupled by T-bet and eomesodermin. Nat. Immunol. 6, 1236-1244 (2005).
12. Pearce, E. L. et al. Control of effector CD8\+ T cell function by the transcription factor Eomesodermin. Science 302, 1041-1043 (2003).
13. Steinman, L. A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat. Med. 13, 139-145 (2007).
14. Sospedra, M., Martin, R. Immunology of multiple sclerosis. Annu. Rev. Immunol. 23, 683-747 (2005).
15. Man, S., Ubogu, E. E., Ransohoff, R. M. Inflammatory cell migration into the central nervous system: a few new twists on an old tale. Brain Pathol. 17, 243-250 (2007).
16. Pierson, E., Simmons, S. B., Castelli, L., Goverman, J. M. Mechanisms regulating regional localization of inflammation during CNS autoimmunity. Immunol. Rev. 248, 205-215 (2012).
17. Gold, R., Linington, C., Lassmann, H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 129, 1953-1971 (2006).
18. Weiner, H. L. The challenge of multiple sclerosis: how do we cure a chronic heterogeneous disease? Ann. Neurol. 65, 239-248 (2009).
19. Lublin, F. D., Reingold, S. C. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46, 907-911 (1996).
20. Lassmann, H., van Horssen, J., Mahad, D. Progressive multiple sclerosis: pathology and pathogenesis. Nat. Rev. Neurol. 8, 647-656 (2012).
21. Wang, T. et al. Granzyme B-induced neurotoxicity is mediated via activation of PAR-1 receptor and Kv1.3 channel. PLoS ONE 7, e43950 (2012).
22. Coquet, J. M. et al. The CD27 and CD70 costimulatory pathway inhibits effector function of T helper 17 cells and attenuates associated autoimmunity. Immunity 38, 53-65 (2013).
23. Rothhammer, V. et al. Th17 lymphocytes traffic to the central nervous system independently of alpha4 integrin expression during EAE. J. Exp. Med. 208, 2465-2476 (2011).
24. Teijaro, J. R. et al. Cutting edge: tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J. Immunol. 187, 5510-5514 (2011).
25. Cheroutre, H., Husain, M. M. CD4 CTL: living up to the challenge. Semin. Immunol. 25, 273-281 (2013).
26. Knox, J. J., Cosma, G. L., Betts, M. R., McLane, L. M. Characterization of T-bet and eomes in peripheral human immune cells. Front. Immunol. 5, 217 (2014).
27. Banerjee, A. et al. Cutting edge: The transcription factor eomesodermin enables CD8\+ T cells to compete for the memory cell niche. J. Immunol. 185, 4988-4992 (2010).
28. Brown, D. M. Cytolytic CD4 cells: direct mediators in infectious disease and malignancy. Cell Immunol. 262, 89-95 (2010).
29. Kebir, H. et al. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat. Med. 13, 1173-1175 (2007).
30. Metkar, S. S. et al. Cytotoxic cell granule-mediated apoptosis: perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation. Immunity 16, 417-428 (2002).
31. Kato, Y. et al. Inhibition of arterial thrombosis by a protease-activated receptor 1 antagonist, FR171113, in the guinea pig. Eur. J. Pharmacol. 473, 163-169 (2003).
32. Patsopoulos, N. A. et al. Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. Ann. Neurol. 70, 897-912 (2011).
33. Curran, M. A. et al. Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of Eomesodermin. J. Exp. Med. 210, 743-755 (2013).
34. Marshall, N. B., Swain, S. L. Cytotoxic CD4 T cells in antiviral immunity. J. Biomed. Biotechnol. 2011, 954602 (2011).
35. Qui, H. Z. et al. CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to program cytotoxic Th1 differentiation. J. Immunol. 187, 3555-3564 (2011).
36. Carboni, S. et al. CD134 plays a crucial role in the pathogenesis of EAE and is upregulated in the CNS of patients with multiple sclerosis. J. Neuroimmunol. 145, 1-11 (2003).
37. Martinez Gomez, J. M. et al. Development of experimental autoimmune encephalomyelitis critically depends on CD137 ligand signaling. J. Neurosci. 32, 18246-18252 (2012).
38. Liu, G. Z. et al. Increased soluble 4-1BB ligand (4-1BBL) levels in peripheral blood of patients with multiple sclerosis. Scand. J. Immunol. 64, 412-419 (2006).
39. Ichiyama, K. et al. Transcription factor Smad-independent T helper 17 cell induction by transforming-growth factor-beta is mediated by suppression of eomesodermin. Immunity 34, 741-754 (2011).
40. Egawa, T., Littman, D. R. ThPOK acts late in specification of the helper T cell lineage and suppresses Runx-mediated commitment to the cytotoxic T cell lineage. Nat. Immunol. 9, 1131-1139 (2008).
41. Reis, B. S., Rogoz, A., Costa-Pinto, F. A., Taniuchi, I., Mucida, D. Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4(\+) T cell immunity. Nat. Immunol. 14, 271-280 (2013).
42. Vacchio, M. S. et al. A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4(\+) T cells. Nat. Immunol. 15, 947-956 (2014).
43. Wang, L. et al. The zinc finger transcription factor Zbtb7b represses CD8-lineage gene expression in peripheral CD4\+ T cells. Immunity 29, 876-887 (2008).
44. Boldison, J. et al. Tissue-resident exhausted effector memory CD8\+ T cells accumulate in the retina during chronic experimental autoimmune uveoretinitis. J. Immunol. 192, 4541-4550 (2014).
45. Lovett-Racke, A. E., Yang, Y., Racke, M. K. Th1 versus Th17: are T cell cytokines relevant in multiple sclerosis? Biochim. Biophys. Acta 1812, 246-251 2011.
46. Milo, R., Miller, A. Revised diagnostic criteria of multiple sclerosis. Autoimmun. Rev. 13, 518-524 (2014).
47. Kanki, H., Suzuki, H., Itohara, S. High-efficiency CAG-FLPe deleter mice in C57BL/6J background. Exp. Anim. 55, 137-141 (2006).
48. Lee, P. P. et al. A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15, 763-774 (2001).
49. Klemann, C., Raveney, B. J., Oki, S., Yamamura, T. Retinoid signals and Th17-mediated pathology. Nihon Rinsho Meneki Gakkai kaishi 32, 20-28 (2009).
50. Klemann, C. et al. Synthetic retinoid AM80 inhibits Th17 cells and ameliorates experimental autoimmune encephalomyelitis. Am. J. Pathol. 174, 2234-2245 (2009).