IL-7 signalling represses Bcl-6 and the T FH gene program

Nature Communications

Volumn 7, Issue , 2016, Pages

  McDonald, Paul W ^a   Read, Kaitlin A ^a   Baker, Chandra E ^a   Anderson, Ashlyn E ^a   Powell, Michael D ^a   Ballesteros Tato, André ^b   Oestreich, Kenneth J ^a,c  

^a VIRGINIA TECH CARILION SCHOOL OF MEDICINE   (United States)

^b The University of Alabama at Birmingham   (United States)

^c VIRGINIA MARYLAND REGIONAL COLLEGE OF VETERINARY MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AQUAPORIN 9; B LYMPHOCYTE INDUCED MATURATION PROTEIN 1; CD27 ANTIGEN; CD40 LIGAND; CHEMOKINE RECEPTOR CCR7; CHEMOKINE RECEPTOR CXCR3; CHEMOKINE RECEPTOR CXCR5; INTERLEUKIN 2; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR ALPHA; INTERLEUKIN 7; INTERLEUKIN 7 RECEPTOR; KRUPPEL LIKE FACTOR 2; KRUPPEL LIKE FACTOR 3; L SELECTIN; PROTEIN BCL 6; SIGNALING LYMPHOCYTE ACTIVATION MOLECULE ASSOCIATED PROTEIN; STAT5 PROTEIN; TRANSCRIPTION FACTOR FKHR; TRANSCRIPTION FACTOR T BET; UNCLASSIFIED DRUG; BCL6 PROTEIN, MOUSE; BLR1 PROTEIN, MOUSE; DNA BINDING PROTEIN; INTERLEUKIN 6 RECEPTOR; KLF2 PROTEIN, MOUSE; KRUPPEL LIKE FACTOR; PRDM1 PROTEIN, MOUSE; TRANSCRIPTION FACTOR;

GENE; INFLUENZA; MEDICAL GEOGRAPHY; SIGNALING;

ANIMAL CELL; ANTIGEN SPECIFICITY; ARTICLE; CD4+ T LYMPHOCYTE; CELL FATE; CELL POPULATION; CELLULAR IMMUNITY; CONTROLLED STUDY; DOWN REGULATION; GENE REPRESSION; HELPER CELL; HUMORAL IMMUNITY; INFLUENZA; LYMPHOCYTE DIFFERENTIATION; MEMORY T LYMPHOCYTE; MOUSE; NONHUMAN; NUCLEAR REPROGRAMMING; PROMOTER REGION; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; T FOLLICULAR HELPER CELL; TH1 CELL; UPREGULATION; ANIMAL; CHROMATIN IMMUNOPRECIPITATION; FLOW CYTOMETRY; GENE EXPRESSION REGULATION; GENETICS; IMMUNOBLOTTING; METABOLISM; ORTHOMYXOVIRUS INFECTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; T LYMPHOCYTE SUBPOPULATION;

ANIMALS; CHROMATIN IMMUNOPRECIPITATION; DNA-BINDING PROTEINS; FLOW CYTOMETRY; GENE EXPRESSION REGULATION; IMMUNOBLOTTING; INTERLEUKIN-2; INTERLEUKIN-6; INTERLEUKIN-7; KRUPPEL-LIKE TRANSCRIPTION FACTORS; L-SELECTIN; MICE; ORTHOMYXOVIRIDAE INFECTIONS; PROTO-ONCOGENE PROTEINS C-BCL-6; RECEPTORS, CXCR5; RECEPTORS, INTERLEUKIN-6; RECEPTORS, INTERLEUKIN-7; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; STAT5 TRANSCRIPTION FACTOR; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, HELPER-INDUCER; TH1 CELLS; TRANSCRIPTION FACTORS;

EID: 84953924620     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms10285     Document Type: Article

References (61)

1. Gasper, D. J., Tejera, M. M. & Suresh, M. CD4 T-cell memory generation and maintenance. Crit. Rev. Immunol. 34, 121-146 (2014).
2. Kaech, S. M. & Cui, W. Transcriptional control of effector and memory CD8(+) T cell differentiation. Nat. Rev. Immunol. 12, 749-761 (2012).
3. Strutt, T. M. et al. Multipronged CD4(+) T-cell effector and memory responses cooperate to provide potent immunity against respiratory virus. Immunol. Rev. 255, 149-164 (2013).
4. Crotty, S. Follicular helper CD4 T cells (T(FH). Annu. Rev. Immunol. 29, 621-663 (2011).
5. Ma, C. S., Deenick, E. K., Batten, M. & Tangye, S. G. The origins, function, and regulation of T follicular helper cells. J. Exp. Med. 209, 1241-1253 (2012).
6. Tangye, S. G., Ma, C. S., Brink, R. & Deenick, E. K. The good, the bad and the ugly-TFH cells in human health and disease. Nat. Rev. Immunol. 13, 412-426 (2013).
7. Crotty, S. T follicular helper cell differentiation, function, and roles in disease. Immunity 41, 529-542 (2014).
8. Moon, H. et al. Early development in the peritoneal cavity of CD49dhigh Th1 memory phenotype CD4+ T cells with enhanced B cell helper activity. J. Immunol. 195, 564-575 (2015).
9. Choi, Y. S. et al. Bcl6 expressing follicular helper CD4 T cells are fate committed early and have the capacity to form memory. J. Immunol. 190, 4014-4026 (2013).
10. Lu, K. T. et al. Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells. Immunity 35, 622-632 (2011).
11. Nakayamada, S. et al. Early Th1 cell differentiation is marked by a Tfh cell-like transition. Immunity 35, 919-931 (2011).
12. Oestreich, K. J., Mohn, S. E. & Weinmann, A. S. Molecular mechanisms that control the expression and activity of Bcl-6 in TH1 cells to regulate flexibility with a TFH-like gene profile. Nat. Immunol. 13, 405-411 (2012).
13. Liu, X. et al. Bcl6 expression specifies the T follicular helper cell program in vivo. J. Exp. Med. 209, 1841-1852 (2012).
14. Johnston, R. J. et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325, 1006-1010 (2009).
15. Nurieva, R. I. et al. Bcl6 mediates the development of T follicular helper cells. Science 325, 1001-1005 (2009).
16. Yu, D. et al. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31, 457-468 (2009).
17. Crotty, S., Johnston, R. J. & Schoenberger, S. P. Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation. Nat. Immunol. 11, 114-120 (2010).
18. Ichii, H. et al. Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells. Nat. Immunol. 3, 558-563 (2002).
19. Pepper, M., Pagan, A. J., Igyarto, B. Z., Taylor, J. J. & Jenkins, M. K. Opposing signals from the Bcl6 transcription factor and the interleukin-2 receptor generate T helper 1 central and effector memory cells. Immunity 35, 583-595 (2011).
20. Ichii, H. et al. Bcl6 is essential for the generation of long-term memory CD4+ T cells. Int. Immunol. 19, 427-433 (2007).
21. Kallies, A. Distinct regulation of effector and memory T-cell differentiation. Immunol. Cell. Biol. 86, 325-332 (2008).
22. Kallies, A., Xin, A., Belz, G. T. & Nutt, S. L. Blimp-1 transcription factor is required for the differentiation of effector CD8(+) T cells and memory responses. Immunity 31, 283-295 (2009).
23. Rutishauser, R. L. et al. Transcriptional repressor Blimp-1 promotes CD8(+) T cell terminal differentiation and represses the acquisition of central memory T cell properties. Immunity 31, 296-308 (2009).
24. Zhu, J. & Paul, W. E. Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol. Rev. 238, 247-262 (2010).
25. Ballesteros-Tato, A. et al. Interleukin-2 inhibits germinal center formation by limiting T follicular helper cell differentiation. Immunity 36, 847-856 (2012).
26. Johnston, R. J., Choi, Y. S., Diamond, J. A., Yang, J. A. & Crotty, S. STAT5 is a potent negative regulator of TFH cell differentiation. J. Exp. Med. 209, 243-250 (2012).
27. Nurieva, R. I. et al. STAT5 negatively regulates T follicular helper (Tfh) cell generation and function. J. Biol. Chem. 287, 11234-11239 (2012).
28. Pipkin, M. E. et al. Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity 32, 79-90 (2010).
29. Stelekati, E. et al. Bystander chronic infection negatively impacts development of CD8(+) T cell memory. Immunity 40, 801-813 (2014).
30. Hale, J. S. et al. Distinct memory CD4+ T cells with commitment to T follicular helper-And T helper 1-cell lineages are generated after acute viral infection. Immunity 38, 805-817 (2013).
31. MacLeod, M. K. et al. Memory CD4 T cells that express CXCR5 provide accelerated help to B cells. J. Immunol. 186, 2889-2896 (2011).
32. Weber, J. P., Fuhrmann, F. & Hutloff, A. T-follicular helper cells survive as long-term memory cells. Eur. J. Immunol. 42, 1981-1988 (2012).
33. Kaech, S. M. & Wherry, E. J. Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection. Immunity 27, 393-405 (2007).
34. Choi, Y. S. et al. LEF-1 and TCF-1 orchestrate T(FH) differentiation by regulating differentiation circuits upstream of the transcriptional repressor Bcl6. Nat. Immunol. 16, 980-990 (2015).
35. Jeannet, G. et al. Essential role of the Wnt pathway effector Tcf-1 for the establishment of functional CD8 T cell memory. Proc. Natl Acad. Sci. USA 107, 9777-9782 (2010).
36. Wu, T. et al. TCF1 is required for the T follicular helper cell response to viral infection. Cell Rep. 12, 2099-2110 (2015).
37. Xu, L. et al. The transcription factor TCF-1 initiates the differentiation of T(FH) cells during acute viral infection. Nat. Immunol. 16, 991-999 (2015).
38. Zhou, X. et al. Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity 33, 229-240 (2010).
39. Oestreich, K. J. et al. Bcl-6 directly represses the gene program of the glycolysis pathway. Nat. Immunol. 15, 957-964 (2014).
40. Liao, W., Lin, J. X., Wang, L., Li, P. & Leonard, W. J. Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages. Nat. Immunol. 12, 551-559 (2011).
41. Li, J., Huston, G. & Swain, S. L. IL-7 promotes the transition of CD4 effectors to persistent memory cells. J. Exp. Med. 198, 1807-1815 (2003).
42. Nurieva, R. I. et al. 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 (2008).
43. Choi, Y. S., Eto, D., Yang, J. A., Lao, C. & Crotty, S. Cutting edge: STAT1 is required for IL-6-mediated Bcl6 induction for early follicular helper cell differentiation. J. Immunol. 190, 3049-3053 (2013).
44. Eto, D. et al. IL-21 and IL-6 are critical for different aspects of B cell immunity and redundantly induce optimal follicular helper CD4 T cell (Tfh) differentiation. PLoS ONE 6, e17739 (2011).
45. Poholek, A. C. et al. In vivo regulation of Bcl6 and T follicular helper cell development. J. Immunol. 185, 313-326 (2010).
46. Carrette, F. & Surh, C. D. IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasis. Semin. Immunol. 24, 209-217 (2012).
47. Cui, G. et al. IL-7-induced glycerol transport and TAG synthesis promotes memory CD8+ T cell longevity. Cell 161, 750-761 (2015).
48. Kim, K. et al. Characterization of an interleukin-7-dependent thymic cell line derived from a p53(-/-) mouse. J. Immunol. Methods 274, 177-184 (2003).
49. Kitano, M. et al. Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity. Immunity 34, 961-972 (2011).
50. Hale, J. S. & Ahmed, R. Memory T follicular helper CD4 T cells. Front. Immunol. 6, 16 (2015).
51. Basso, K. & Dalla-Favera, R. BCL6: master regulator of the germinal center reaction and key oncogene in B cell lymphomagenesis. Adv. Immunol. 105, 193-210 (2010).
52. Phan, R. T., Saito, M., Basso, K., Niu, H. & Dalla-Favera, R. BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells. Nat. Immunol. 6, 1054-1060 (2005).
53. Martins, G. & Calame, K. Regulation and functions of Blimp-1 in T and B lymphocytes. Annu. Rev. Immunol. 26, 133-169 (2008).
54. Liao, W., Lin, J. X. & Leonard, W. J. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr. Opin. Immunol. 23, 598-604 (2011).
55. Rochman, Y., Spolski, R. & Leonard, W. J. New insights into the regulation of T cells by gamma(c) family cytokines. Nat. Rev. Immunol. 9, 480-490 (2009).
56. Mandal, M. et al. Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2. Nat. Immunol. 12, 1212-1220 (2011).
57. Choi, Y. S., Yang, J. A. & Crotty, S. Dynamic regulation of Bcl6 in follicular helper CD4 T (Tfh) cells. Curr. Opin. Immunol. 25, 366-372 (2013).
58. Phan, R. T. & Dalla-Favera, R. The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature 432, 635-639 (2004).
59. Ranuncolo, S. M. et al. Bcl-6 mediates the germinal center B cell phenotype and lymphomagenesis through transcriptional repression of the DNA-damage sensor ATR. Nat. Immunol. 8, 705-714 (2007).
60. Lee, J. Y. et al. The transcription factor KLF2 restrains CD4(+) T follicular helper cell differentiation. Immunity 42, 252-264 (2015).
61. Weber, J. P. et al. ICOS maintains the T follicular helper cell phenotype by down-regulating Kruppel-like factor 2. J. Exp. Med. 212, 217-233 (2015).