Transcriptional repressor BCL6 controls Th17 responses by controlling gene expression in both T cells and macrophages

Journal of Immunology

Volumn 184, Issue 8, 2010, Pages 4123-4132

  Mondal, Arpita ^a   Sawant, Deepali ^a   Dent, Alexander L ^a  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 17; INTERLEUKIN 23; INTERLEUKIN 4; INTERLEUKIN 6; PROTEIN BCL 6; RAG1 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; BCL6 PROTEIN, MOUSE; DNA BINDING PROTEIN; IL17A PROTEIN, MOUSE; REPRESSOR PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CD4+ T LYMPHOCYTE; CELL ACTIVITY; CYTOKINE PRODUCTION; GENE EXPRESSION; LYMPHOCYTE CULTURE; LYMPHOCYTE DIFFERENTIATION; MACROPHAGE; MEMORY T LYMPHOCYTE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; TH1 CELL; TH17 CELL; TH2 CELL; UPREGULATION; ANIMAL; BIOSYNTHESIS; C57BL MOUSE; CELL DIFFERENTIATION; COMPARATIVE STUDY; DOWN REGULATION; GENETIC TRANSCRIPTION; GENETICS; HOSPITALIZATION; IMMUNOLOGY; IMMUNOPHENOTYPING; INFLAMMATION; METABOLISM; MOUSE MUTANT; PATHOLOGY; PHYSIOLOGY; T LYMPHOCYTE SUBPOPULATION;

ANIMALS; CELL DIFFERENTIATION; DNA-BINDING PROTEINS; DOWN-REGULATION; IMMUNOPHENOTYPING; INFLAMMATION; INTERLEUKIN-17; MACROPHAGES; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; REPRESSOR PROTEINS; SEVERITY OF ILLNESS INDEX; T-LYMPHOCYTE SUBSETS; TRANSCRIPTION, GENETIC; UP-REGULATION;

EID: 77952780554     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0901242     Document Type: Article

References (41)

1. Iwakura, Y., and H. Ishigame. 2006. The IL-23/IL-17 axis in inflammation. J. Clin. Invest. 116: 1218-1222.
2. Afzali, B., G. Lombardi, R. I. Lechler, and G. M. Lord. 2007. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin. Exp. Immunol. 148: 32-46.
3. Dong, C. 2008. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat. Rev. Immunol. 8: 337-348.
4. Ye, P., F. H. Rodriguez, S. Kanaly, K. L. Stocking, J. Schurr, P. Schwarzenberger, P. Oliver, W. Huang, P. Zhang, J. Zhang, et al. 2001. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Exp. Med. 194: 519-527.
5. Happel, K. I., P. J. Dubin, M. Zheng, N. Ghilardi, C. Lockhart, L. J. Quinton, A. R. Odden, J. E. Shellito, G. J. Bagby, S. Nelson, and J. K. Kolls. 2005. Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J. Exp. Med. 202: 761-769.
6. Stritesky, G. L., N. Yeh, and M. H. Kaplan. 2008. IL-23 promotes maintenance but not commitment to the Th17 lineage. J. Immunol. 181: 5948-5955.
7. McGeachy, M. J., Y. Chen, C. M. Tato, A. Laurence, B. Joyce-Shaikh, W. M. Blumenschein, T. K. McClanahan, J. J. O'Shea, and D. J. Cua. 2009. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat. Immunol. 10: 314-324.
8. Lee, Y. K., H. Turner, C. L. Maynard, J. R. Oliver, D. Chen, C. O. Elson, and C. T. Weaver. 2009. Late developmental plasticity in the T helper 17 lineage. Immunity 30: 92-107.
9. Mathur, A. N., H. C. Chang, D. G. Zisoulis, G. L. Stritesky, Q. Yu, J. T. O'Malley, R. Kapur, D. E. Levy, G. S. Kansas, and M. H. Kaplan. 2007. Stat3 and Stat4 direct development of IL-17-secreting Th cells. J. Immunol. 178: 4901-4907.
10. Ivanov, I. I., B. S. McKenzie, L. Zhou, C. E. Tadokoro, A. Lepelley, J. J. Lafaille, D. J. Cua, and D. R. Littman. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126: 1121-1133.
11. Zhou, L., I. I. Ivanov, R. Spolski, R. Min, K. Shenderov, T. Egawa, D. E. Levy, W. J. Leonard, and D. R. Littman. 2007. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat. Immunol. 8: 967-974.
12. Nurieva, R., X. O. Yang, G. Martinez, Y. Zhang, A. D. Panopoulos, L. Ma, K. Schluns, Q. Tian, S. S. Watowich, A. M. Jetten, and C. Dong. 2007. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448: 480-483. (Pubitemid 47123514)
13. Korn, T., E. Bettelli, W. Gao, A. Awasthi, A. Jäger, T. B. Strom, M. Oukka, and V. K. Kuchroo. 2007. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448: 484-487. (Pubitemid 47123515)
14. Laurence, A., C. M. Tato, T. S. Davidson, Y. Kanno, Z. Chen, Z. Yao, R. B. Blank, F. Meylan, R. Siegel, L. Hennighausen, et al. 2007. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26: 371-381. (Pubitemid 46413906)
15. Mathur, A. N., H. C. Chang, D. G. Zisoulis, R. Kapur, M. L. Belladonna, G. S. Kansas, and M. H. Kaplan. 2006. T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype. Blood 108: 1595-1601.
16. Seyfert, V. L., D. Allman, Y. He, and L. M. Staudt. 1996. Transcriptional repression by the proto-oncogene BCL-6. Oncogene 12: 2331-2342.
17. Ye, B. H., F. Lista, F. Lo Coco, D. M. Knowles, K. Offit, R. S. Chaganti, and R. Dalla-Favera. 1993. Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma. Science 262: 747-750.
18. Staudt, L. M., A. L. Dent, A. L. Shaffer, and X. Yu. 1999. Regulation of lymphocyte cell fate decisions and lymphomagenesis by BCL-6. Int. Rev. Immunol. 18: 381-403.
19. Chang, C. C., B. H. Ye, R. S. Chaganti, and R. Dalla-Favera. 1996. BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor. Proc. Natl. Acad. Sci. USA 93: 6947-6952.
20. Dhordain, P., O. Albagli, R. J. Lin, S. Ansieau, S. Quief, A. Leutz, J. P. Kerckaert, R. M. Evans, and D. Leprince. 1997. Corepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein. Proc. Natl. Acad. Sci. USA 94: 10762-10767.
21. Huynh, K. D., W. Fischle, E. Verdin, and V. J. Bardwell. 2000. BCoR, a novel corepressor involved in BCL-6 repression. Genes Dev. 14: 1810-1823.
22. Huynh, K. D., and V. J. Bardwell. 1998. The BCL-6 POZ domain and other POZ domains interact with the co-repressors N-CoR and SMRT. Oncogene 17: 2473-2484.
23. Onizuka, T., M. Moriyama, T. Yamochi, T. Kuroda, A. Kazama, N. Kanazawa, K. Sato, T. Kato, H. Ota, and S. Mori. 1995. BCL-6 gene product, a 92- to 98-kD nuclear phosphoprotein, is highly expressed in germinal center B cells and their neoplastic counterparts. Blood 86: 28-37.
24. Cattoretti, G., C. C. Chang, K. Cechova, J. Zhang, B. H. Ye, B. Falini, D. C. Louie, K. Offit, R. S. Chaganti, and R. Dalla-Favera. 1995. BCL-6 protein is expressed in germinal-center B cells. Blood 86: 45-53.
25. Dent, A. L., A. L. Shaffer, X. Yu, D. Allman, and L. M. Staudt. 1997. Control of inflammation, cytokine expression, and germinal center formation by BCL-6. Science 276: 589-592.
26. Ye, B. H., G. Cattoretti, Q. Shen, J. Zhang, N. Hawe, R. de Waard, C. Leung, M. Nouri-Shirazi, A. Orazi, R. S. Chaganti, et al. 1997. The BCL-6 protooncogene controls germinal-centre formation and Th2-type inflammation. Nat. Genet. 16: 161-170.
27. Yoshida, T., T. Fukuda, M. Hatano, H. Koseki, S. Okabe, K. Ishibashi, S. Kojima, M. Arima, I. Komuro, G. Ishii, et al. 1999. The role of Bcl6 in mature cardiac myocytes. Cardiovasc. Res. 42: 670-679.
28. Kusam, S., L. M. Toney, H. Sato, and A. L. Dent. 2003. Inhibition of Th2 differentiation and GATA-3 expression by BCL-6. J. Immunol. 170: 2435-2441. (Pubitemid 36245631)
29. Dent, A. L., J. Hu-Li, W. E. Paul, and L. S. Staudt. 1998. T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6. Proc. Natl. Acad. Sci. USA 95: 13823-13828.
30. Nurieva, R. I., Y. Chung, G. J. Martinez, X. O. Yang, S. Tanaka, T. D. Matskevitch, Y. H. Wang, and C. Dong. 2009. Bcl6 mediates the development of T follicular helper cells. Science 325: 1001-1005.
31. Yu, D., S. Rao, L. M. Tsai, S. K. Lee, Y. He, E. L. Sutcliffe, M. Srivastava, M. Linterman, L. Zheng, N. Simpson, et al. 2009. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31: 457-468.
32. Johnston, R. J., A. C. Poholek, D. DiToro, I. Yusuf, D. Eto, B. Barnett, A. L. Dent, J. Craft, and S. Crotty. 2009. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325: 1006-1010.
33. Toney, L. M., G. Cattoretti, J. A. Graf, T. Merghoub, P. P. Pandolfi, R. Dalla-Favera, B. H. Ye, and A. L. Dent. 2000. BCL-6 regulates chemokine gene transcription in macrophages. Nat. Immunol. 1: 214-220.
34. Yu, R. Y., X. Wang, F. J. Pixley, J. J. Yu, A. L. Dent, H. E. Broxmeyer, E. R. Stanley, and B. H. Ye. 2005. BCL-6 negatively regulates macrophage proliferation by suppressing autocrine IL-6 production. Blood 105: 1777-1784.
35. Lund, R. J., E. K. Ylikoski, T. Aittokallio, O. Nevalainen, and R. Lahesmaa. 2003. Kinetics and STAT4- or STAT6-mediated regulation of genes involved in lymphocyte polarization to Th1 and Th2 cells. Eur. J. Immunol. 33: 1105-1116.
36. Chtanova, T., S. G. Tangye, R. Newton, N. Frank, M. R. Hodge, M. S. Rolph, and C. R. Mackay. 2004. T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J. Immunol. 173: 68-78. (Pubitemid 38797327)
37. Fazilleau, N., L. J. McHeyzer-Williams, H. Rosen, and M. G. McHeyzer-Williams. 2009. The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding. Nat. Immunol. 10: 375-384.
38. Nurieva, R. I., Y. Chung, D. Hwang, X. O. Yang, H. S. Kang, L. Ma, Y. H. Wang, S. S. Watowich, A. M. Jetten, Q. Tian, and C. Dong. 2008. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 29: 138-149.
39. Gorelik, L., P. E. Fields, and R. A. Flavell. 2000. Cutting edge: TGF-beta inhibits Th type 2 development through inhibition of GATA-3 expression. J. Immunol. 165: 4773-4777.
40. Heath, V. L., E. E. Murphy, C. Crain, M. G. Tomlinson, and A. O'Garra. 2000. TGF-beta1 down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression. Eur. J. Immunol. 30: 2639-2649.
41. Takeda, N., M. Arima, N. Tsuruoka, S. Okada, M. Hatano, A. Sakamoto, Y. Kohno, and T. Tokuhisa. 2003. Bcl6 is a transcriptional repressor for the IL-18 gene. J. Immunol. 171: 426-431. (Pubitemid 36745316)