World Allergy Organization Journal | |
Role of the Transcriptional Repressor BCL6 in Allergic Response and Inflammation | |
Takeshi Tokuhisa1  Takeshi Fukuda2  Masafumi Arima1  | |
[1] Department of Developmental Genetics, Chiba University Graduate School of Medicine, Chiba;Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Dokkyo, Japan | |
关键词: transcriptional repressor; Th2; lgE; chemokine; cytokine; BCL6; allergy; | |
Others : 824526 DOI : 10.1097/WOX.0b013e31817dc522 |
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received in 2008-03-28, accepted in 2008-04-25, 发布年份 2008 | |
【 摘 要 】
Various molecules participate in different phases of allergic reactions. This means that many genes are encoding molecules related to allergic reactions, such as cytokines, chemokines, and their receptors as effector molecules. The transcriptional repressor BCL6 has emerged as a multifunctional regulator of lymphocyte differentiation and immune responses. BCL6-deficient (BCL-/-) mice display T helper type 2 (Th2)-type inflammation, which is caused by abnormality of both lymphoid cells and nonlymphoid cells. Thus, BCL6 apparently contributes to negative regulation of various central molecules such as cytokines, in particular Th2 cytokines, CC chemokines, and immunoglobulin E in allergic diseases. Therefore, BCL6 may be a molecular target for Th2-type allergic diseases.
【 授权许可】
2008 World Allergy Organization; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Dalla-Favera R, Migliazza A, Chang CC, Niu H, Pasqualucci L, Butler M, et al.: Molecular pathogenesis of B cell malignancy: the role of BCL-6. Curr Top Microbiol Immunol 1999, 246:257-263.
- [2]Staudt LM, Dent AL, Shaffer AL, Yu X: Regulation of lymphocyte cell fate decisions and lymphomagenesis by BCL-6. Int J Immunol 1999, 18:381-403.
- [3]Dent AL, Shaffer AL, Yu X, Allman D, Staudt LM: Control of inflammation, cytokine expression, and germinal center formation by BCL-6. Science 1997, 276:589-592.
- [4]Fukuda T, Yoshida T, Okada S, Hatano M, Miki T, Ishibashi K, et al.: Disruption of the Bcl6 gene results in an impaired germinal center formation. J Exp Med 1997, 186:439-448.
- [5]Ye BH, Cattoretti G, Shen Q, Zhang J, Hawe N, de Waard R, et al.: The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation. Nat Genet 1997, 16:161-170.
- [6]Kerchaert JP, Deweindt C, Tilly H, Quief S, Lecocq G, Bastard C: LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas. Nat Genet 1993, 5:66-70.
- [7]Ye BH, Lista F, Lo Coco F, Knowles DM, Offit K, Chaganti RS, et al.: Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma. Science 1993, 262:747-750.
- [8]Miki T, Kawamata N, Hirosawa S, Aoki N: Gene involved in the 3q27 translocation associated with B-cell lymphoma, BCL5, encodes a Krüppel like zinc-finger protein. Blood 1994, 83:26-32.
- [9]Cattoretti G, Chang CC, Cechova K, Zhang J, Ye BH: BCL-6 protein is expressed in germinal-center B cells. Blood 1995, 86:45-53.
- [10]Yamochi T, Kitabayashi A, Hirokawa M, Miura AB, Onizuka T, Mori S, et al.: Regulation of BCL-6 gene expression in human myeloid/monocytoid leukemic cells. Leukemia 1997, 11:694-700.
- [11]Baron BW, Stanger RR, Hume E, Sadhu A, Mick R, Kerckaert JP, et al.: BCL6 encodes a sequence-specific DNA-binding protein. Genes Chromosomes Cancer 1995, 13:221-224.
- [12]Seyfert VL, Allman D, He Y, Staudt LM: Transcriptional repression by the proto-oncogene BCL-6. Oncogene 1996, 12:2331-2342.
- [13]Gupta S, Jiang M, Anthony A, Pernis AB: Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4. J Exp Med 1999, 190:1837-1848.
- [14]Harris MB, Chang CC, Berton MT, Danial NN, Zhang J, Kuehner D, et al.: Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching. Mol Cell Biol 1999, 19:7264-7275.
- [15]Arima M, Toyama H, Ichii H, Kojima S, Okada S, Hatano M, et al.: A putative silencer element in the IL-5 gene recognized by Bcl6. J Immunol 2002, 169:829-836.
- [16]Kusam S, Toney LM, Sato H, Dent AL: Inhibition of Th2 differentiation and GATA-3 expression by BCL-6. J Immunol 2003, 170:2435-2441.
- [17]Takeda N, Arima M, Tsuruoka N, Okada S, Hatano M, Sakamoto A, et al.: Bcl6 is a transcriptional repressor for the IL-18 gene. J Immunol 2003, 171:426-431.
- [18]Yu RY, Wang X, Pixley FJ, Yu JJ, Dent AL, Broxmeyer HE, et al.: BCL-6 negatively regulates macrophage proliferation by suppressing autocrine IL-6 production. Blood 2005, 105:1777-1784.
- [19]Toney LM, Cattoretti G, Graf JA, Merghoub T, Pandolfi PP, Dalla-Favera R, et al.: BCL-6 regulates chemokine gene transcription in macrophages. Nat Immunol 2000, 1:214-220.
- [20]Shaffer AL, Yu X, He Y, Boldrick J, Chan EP, Staudt LM: BCL-6 represses genes that function in lymphocyte differentiation, inflammation and cell cycle control. Immunity 2000, 13:199-212.
- [21]Niu H, Cattoretti G, Dalla-Favera R: BCL6 controls the expression of the B7-1/CD80 costimulatory receptor in germinal center B cells. J Exp Med 2003, 198:211-221.
- [22]Phan RT, 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 2005, 6:1054-1060.
- [23]Phan RT, Dalla-Favera R: The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature 2004, 432:635-659.
- [24]Shvarts A, Brummelkamp TR, Scheeren F, Koh E, Daley GQ, Spits H, et al.: A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19(ARF)-p53 signaling. Genes Dev 2002, 16:681-686.
- [25]Ranuncolo SM, Polo JM, Dierov J, Singer M, Kuo T, Greally J, et al.: Bcl-6 mediates the germinal center B cell phenotype and lymphomagenesis through transcriptional repression of the DNA-damage sensor ATR. Nat Immunol 2007, 8:705-714.
- [26]Baron BW, Zeleznik-Le N, Baron MJ, Theisler C, Huo D, Krasowski MD, et al.: Repression of the PDCD2 gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas. Proc Natl Acad Sci USA 2007, 104:7449-7454.
- [27]Baron BW, Anastasi J, Thirman MJ, Furukawa Y, Fears S, Kim DC, et al.: The human programmed cell death-2 (PDCD2) gene is a target of BCL6 repression: implications for a role of BCL6 in the down-regulation of apoptosis. Proc Natl Acad Sci USA 2002, 99:2860-2865.
- [28]Tang TT, Dowbenko D, Jackson A, Toney L, Lewin DA, Dent AL, et al.: The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor. J Biol Chem 2002, 277:14255-14265.
- [29]Li Z, Wang X, Yu RY, Ding BB, Yu JJ, Dai XM, et al.: BCL-6 negatively regulates expression of the NF-kappaB1 p105/p50 subunit. J Immunol 2005, 174:205-214.
- [30]Harris MB, Mostecki J, Rothman PB: Repression of an interleukin-4-responsive promoter requires cooperative BCL-6 function. Biol Chem 2005, 280:13114-13121.
- [31]Harris MB, Chang CC, Berton MT, Danial NN, Zhang J, Kuehner D, et al.: Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching. Mol Cell Biol 1999, 19:7264-7275.
- [32]Albagli O, Lantoine D, Quief S, Quignon F, Englert C, Kerckaert JP, et al.: Overexpressed BCL6 (LAZ3) oncoprotein triggers apoptosis, delays S phase progression and associates with replication foci. Oncogene 1999, 18:5063-5075.
- [33]Yamochi T, Kaneita Y, Akiyama T, Mori S, Moriyama M: Adenovirus-mediated high expression of BCL-6 in CV-1 cells induces apoptotic cell death accompanied by down-regulation of BCL-2 and BCL-X(L). Oncogene 1999, 18:487-494.
- [34]Toyama H, Okada S, Hatano M, Takahashi Y, Takeda N, Ichii H, et al.: Memory B cells without somatic hypermutation are generated from Bcl6-deficient B cells. Immunity 2002, 17:329-339.
- [35]Ichii H, Sakamoto A, Hatano M, Okada S, Toyama H, Taki S, et al.: Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells. Nat Immunol 2002, 3:558-563.
- [36]Ichii H, Sakamoto A, Kuroda Y, Tokuhisa T: Bcl6 acts as an amplifier for the generation and proliferative capacity of central memory CD8+ T Cells. J Immunol 2004, 173:883-891.
- [37]Ichii H, Sakamoto A, Arima M, Hatano M, Kuroda Y, Tokuhisa T: Bcl6 is essential for the generation of long-term memory CD4+ T cells. Int Immunol 2007, 19:427-433.
- [38]Allman D, Jain A, Dent A, Maile RR, Selvaggi T, Kehry MR, et al.: BCL-6 expression during B-cell activation. Blood 1996, 87:5257-5268.
- [39]Fero ML, Rivkin M, Tasch M, Porter P, Carow CE, Firpo E, et al.: A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice. Cell 1996, 85:733-744.
- [40]Fero ML, Randel E, Gurley KE, Roberts JM, Kemp CJ: The murine gene p27Kip1 is haplo-insufficient for tumour suppression. Nature 1998, 396:177-180.
- [41]Arguni E, Arima M, Tsuruoka N, Sakamoto A, Hatano M, Tokuhisa T: JunD/AP-1 and STAT3 are the major enhancer molecules for high Bcl6 expression in germinal center B cells. Int Immunol 2006, 18:1079-1089.
- [42]Kitayama D, Sakamoto A, Arima M, Hatano M, Miyazaki M, Tokuhisa T: A role for Bcl6 in sequential class switch recombination to IgE in B cells stimulated with IL-4 and IL-21. Mol Immunol 2008, 45:1337-1345.
- [43]Yoshida T, Fukuda T, Hatano M, Koseki H, Okabe S, Ishibashi K, et al.: A role of Bcl6 in mature cardiac myocytes. Cardiovasc Res 1999, 42:670-679.
- [44]Lund R, Ahlfors H, Kainonen E, Lahesmaa AM, Dixon C, Lahesmaa R: Identification of genes involved in the initiation of human Th1 or Th2 cell commitment. Eur J Immunol 2005, 35:3307-3319.
- [45]Lund RJ, Ylikoski EK, Aittokallio T, Nevalainen O, Lahesmaa R: Kinetics and STAT4- or STAT6-mediated regulation of genes involved in lymphocyte polarization to Th1 and Th2 cells. Eur J Immunol 2003, 33:1105-1116.
- [46]Zhou G, Ono SJ: Induction of BCL-6 gene expression by interferon-gamma and identification of an IRE in exon I. Exp Mol Pathol 2005, 78:25-35.
- [47]Kaplan MH, Schindler U, Smiley ST, Grusby MJ: Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 1996, 4:313-319.
- [48]Dent AL, Hu-Li J, Paul WE, Staudt LM: T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6. Proc Natl Acad Sci USA 1998, 95:13823-13828.
- [49]Yamaguchi Y, Hayashi Y, Sugama Y, Miura Y, Kasahara T, Kitamura S, et al.: Highly purified murine interleukin 5 (IL-5) stimulates eosinophil function and prolongs in vitro survival. IL-5 as an eosinophil chemotactic factor. J Exp Med 1988, 167:1737-1742.
- [50]Karpus WJ, Lukacs NW, Kennedy KJ, Smith WS, Hurst SD, Barrett TA: Differential CC chemokine-induced enhancement of T helper cell cytokine production. J Immunol 1997, 158:4129-4136.
- [51]Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ: Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 2000, 404:407-411.
- [52]Braun MC, Lahey E, Kelsall BL: Selective suppression of IL-12 production by chemoattractants. J Immunol 2000, 164:3009-3017.
- [53]Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, et al.: Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 1995, 378:88-91.
- [54]Nakanishi K, Yoshimoto T, Tsutsi H, Okamura H: Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev 2001, 12:53-72.
- [55]Sugimoto T, Ishikawa Y, Yoshimoto T, Hayashi N, Fujimoto J, Nakanishi K: Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse. J Exp Med 2004, 199:535-545.
- [56]El-Mezzein RE, Matsumoto T, Nomiyama H, Miike T: Increased secretion of IL-18 in vitro by peripheral blood mononuclear cells of patients with bronchial asthma and atopic dermatitis. J Clin Immunol 2001, 126:193-198.
- [57]Yoshizawa Y, Nomaguchi H, Izaki S, Kitamura K: Serum cytokine levels in atopic dermatitis. Clin Exp Dermatol 2002, 27:225-229.
- [58]Wong CK, Ho CY, Ko FW, Chan CH, Ho AS, Hui DS, et al.: Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-g, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin Exp Immunol 2001, 125:177-183.
- [59]Tanaka H, Miyazaki N, Oashi K, Teramoto S, Shiratori M, Hashimoto M, et al.: IL-18 might reflect disease activity in mild and moderate asthma exacerbation. J Allergy Clin Immunol 2001, 107:331-336.
- [60]Higashi N, Gesser B, Kawana S, Thestrup-Pedersen K: Expression of IL-18 mRNA and secretion of IL-18 are reduced in monocytes from patients with atopic dermatitis. J Allergy Clin Immunol 2001, 108:607-614.
- [61]Verhaeghe B, Gevaert P, Holtappels G, Lukat KF, Lange B, Van Cauwenberge P, et al.: Up-regulation of IL-18 in allergic rhinitis. Allergy 2002, 57:825-830.
- [62]Levi-Schaffer F, Temkin V, Malamud V, Feld S, Zilberman Y: Mast cells enhance eosinophil survival in vitro: role of TNF-alpha and granulocytemacrophage colony-stimulating factor. J Immunol 1998, 160:5554-5562.
- [63]Skokos S, Le Panse S, Villa I, Rousselle JC, Peronet R, David B, et al.: Mast cell-dependent B and T lymphocyte activation is mediated by the secretion of immunologically active exosomes. J Immunol 2001, 166:868-876.
- [64]Skokos D, Botros HG, Demeure C, Morin J, Peronet R, Birkenmeier G, et al.: Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo. J Immunol 2003, 170:3037-3045.
- [65]Schmitz J, Thiel A, Kuhn R, Rajewsky K, Muller W, Assenmacher M, et al.: Induction of interleukin 4 (IL-4) expression in T helper (Th) cells is not dependent on IL-4 from non-Th cells. J Exp Med 1994, 179:1349-1353.
- [66]Fallon PG, Jolin HE, Smith P, Emson CL, Townsend MJ, Fallon R, et al.: IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13. Immunity 2002, 17:7-17.
- [67]Nakajima T, Inagaki N, Tanaka H, Tanaka A, Yoshikawa M, Tamari M, et al.: Marked increase in CC chemokine gene expression in both human and mouse mast cell transcriptomes following Fcepsilon receptor I cross-linking: an interspecies comparison. Blood 2002, 100:3861-3868.
- [68]McKenzie GJ, Emson CL, Bell SE, Anderson S, Fallon P, Zurawski G, et al.: Impaired development of Th2 cells in IL-13-deficient mice. Immunity 1998, 9:423-432.
- [69]Chiaramonte G, Donaldson DD, Cheever AW, Wynn TA: An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. J Clin Invest 1999, 104:777-785.
- [70]Adra CN, Gao PS, Mao XQ, Baron BW, Pauker S, Miki T, et al.: Variants of B cell lymphoma 6 (BCL6) and marked atopy. Clin Genet 1998, 54:362-364.
- [71]O'Garra A: Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 1998, 8:275-283.