IMMUNE NETWORK

  • 제11권1호
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  • Pages.1-10
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  • 2011
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  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
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Seeing is Believing: Illuminating the Source of In Vivo Interleukin-7

  • Kim, Grace Yoon-Hee (Experimental Immunology Branch, National Cancer Institute, National Institutes of Health) ;
  • Hong, Chang-Wan (Experimental Immunology Branch, National Cancer Institute, National Institutes of Health) ;
  • Park, Jung-Hyun (Experimental Immunology Branch, National Cancer Institute, National Institutes of Health)
  • 투고 : 2011.02.07
  • 심사 : 2011.02.11
  • 발행 : 2011.02.28
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⟨ 이전 논문 다음 논문 ⟩

초록

Interleukin-7 (IL-7) is an essential cytokine for T cells. However, IL-7 is not produced by T cells themselves such that T cells are dependent on extrinsic IL-7. In fact, in the absence of IL-7, T cell development in the thymus as well as survival of naive T cells in the periphery is severely impaired. Furthermore, modulating IL-7 availability in vivo either by genetic means or other experimental approaches determines the size, composition and function of the T cell pool. Consequently, understanding IL-7 expression is critical for understanding T cell immunity. Until most recently, however, the spatiotemporal expression of in vivo IL-7 has remained obscured. Shortage of such information was partly due to scarce expression of IL-7 itself but mainly due to the lack of adequate reagents to monitor IL-7 expression in vivo. This situation dramatically changed with a recent rush of four independent studies that describe the generation and characterization of IL-7 reporter mice, all utilizing bacterial artificial chromosome transgene technology. The emerging consensus of these studies confirmed thymic stromal cells as the major producers of IL-7 but also identified IL-7 reporter activities in various peripheral tissues including skin, intestine and lymph nodes. Strikingly, developmental and environmental cues actively modulated IL-7 reporter activities in vivo suggesting that IL-7 regulation might be a new mechanism of shaping T cell development and homeostasis. Collectively, the availability of these new tools opens up new venues to assess unanswered questions in IL-7 biology in T cells and beyond.

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참고문헌

  1. Namen AE, Schmierer AE, March CJ, Overell RW, Park LS, Urdal DL, Mochizuki DY: B cell precursor growth-promoting activity. Purification and characterization of a growth factor active on lymphocyte precursors. J Exp Med 167; 988-1002, 1988 https://doi.org/10.1084/jem.167.3.988
  2. Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E, Gliniak BC, Park LS, Ziegler SF, Williams DE, Ware CB, Meyer JD, Davison BL: Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med 180;1955-1960, 1994 https://doi.org/10.1084/jem.180.5.1955
  3. von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R: Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med 181;1519-1526, 1995 https://doi.org/10.1084/jem.181.4.1519
  4. Schluns KS, Kieper WC, Jameson SC, Lefrancois L: Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo. Nat Immunol 21;426-432, 2000
  5. Tan JT, Dudl E, LeRoy E, Murray R, Sprent J, Weinberg KI, Surh CD: IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A 98;8732-8737, 2001 https://doi.org/10.1073/pnas.161126098
  6. Park JH, Adoro S, Guinter T, Erman B, Alag AS, Catalfamo M, Kimura MY, Cui Y, Lucas PJ, Gress RE, Kubo M, Hennighausen L, Feigenbaum L, Singer A: Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic- lineage T cells. Nat Immunol 11;257-264, 2010 https://doi.org/10.1038/ni.1840
  7. Puel A, Ziegler SF, Buckley RH, Leonard WJ: Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency. Nat Genet 20;394-397, 1998 https://doi.org/10.1038/3877
  8. Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ: Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 73;147-157, 1993 https://doi.org/10.1016/0092-8674(93)90167-O
  9. Witte PL, Burrows PD, Kincade PW, Cooper MD: Characterization of B lymphocyte lineage progenitor cells from mice with severe combined immune deficiency disease (SCID) made possible by long term culture. J Immunol 138;2698- 2705, 1987
  10. Akashi K, Kondo M, von Freeden-Jeffry U, Murray R, Weissman IL: Bcl-2 rescues T lymphopoiesis in interleukin- 7 receptor-deficient mice. Cell 89;1033-1041, 1997 https://doi.org/10.1016/S0092-8674(00)80291-3
  11. Opferman JT, Letai A, Beard C, Sorcinelli MD, Ong CC, Korsmeyer SJ: Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature 426;671- 676, 2003 https://doi.org/10.1038/nature02067
  12. Wofford JA, Wieman HL, Jacobs SR, Zhao Y, Rathmell JC: IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival. Blood 111;2101-2111, 2008 https://doi.org/10.1182/blood-2007-06-096297
  13. Vivien L, Benoist C, Mathis D: T lymphocytes need IL-7 but not IL-4 or IL-6 to survive in vivo. Int Immunol 13;763-768, 2001 https://doi.org/10.1093/intimm/13.6.763
  14. Rathmell JC, Farkash EA, Gao W, Thompson CB: IL-7 enhances the survival and maintains the size of naive T cells. J Immunol 167;6869-6876, 2001 https://doi.org/10.4049/jimmunol.167.12.6869
  15. Surh CD, Sprent J: Homeostasis of naive and memory T cells. Immunity 29;848-862, 2008 https://doi.org/10.1016/j.immuni.2008.11.002
  16. Ku CC, Murakami M, Sakamoto A, Kappler J, Marrack P: Control of homeostasis of CD8+ memory T cells by opposing cytokines. Science 288;675-678, 2000 https://doi.org/10.1126/science.288.5466.675
  17. Tan JT, Ernst B, Kieper WC, LeRoy E, Sprent J, Surh CD: Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J Exp Med 195;1523-1532, 2002 https://doi.org/10.1084/jem.20020066
  18. Kieper WC, Tan JT, Bondi-Boyd B, Gapin L, Sprent J, Ceredig R, Surh CD: Overexpression of interleukin (IL)-7 leads to IL-15-independent generation of memory phenotype CD8+ T cells. J Exp Med 195;1533-1539, 2002 https://doi.org/10.1084/jem.20020067
  19. Schluns KS, Williams K, Ma A, Zheng XX, Lefrancois L: Cutting edge: requirement for IL-15 in the generation of primary and memory antigen-specific CD8 T cells. J Immunol 168;4827-4831, 2002 https://doi.org/10.4049/jimmunol.168.10.4827
  20. Rochman Y, Spolski R, Leonard WJ: New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol 9;480-490, 2009 https://doi.org/10.1038/nri2580
  21. Witthuhn BA, Silvennoinen O, Miura O, Lai KS, Cwik C, Liu ET, Ihle JN: Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells. Nature 370;153-157, 1994 https://doi.org/10.1038/370153a0
  22. Maraskovsky E, O'Reilly LA, Teepe M, Corcoran LM, Peschon JJ, Strasser A: Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1−/− mice. Cell 89;1011-1019, 1997 https://doi.org/10.1016/S0092-8674(00)80289-5
  23. Chehtane M, Khaled AR: Interleukin-7 mediates glucose utilization in lymphocytes through transcriptional regulation of the hexokinase II gene. Am J Physiol Cell Physiol 298; C1560-1571, 2010 https://doi.org/10.1152/ajpcell.00506.2009
  24. Khaled AR, Bulavin DV, Kittipatarin C, Li WQ, Alvarez M, Kim K, Young HA, Fornace AJ, Durum SK: Cytokine-driven cell cycling is mediated through Cdc25A. J Cell Biol 169; 755-763, 2005 https://doi.org/10.1083/jcb.200409099
  25. Jiang Q, Li WQ, Aiello FB, Mazzucchelli R, Asefa B, Khaled AR, Durum SK: Cell biology of IL-7, a key lymphotrophin. Cytokine Growth Factor Rev 16;513-533, 2005 https://doi.org/10.1016/j.cytogfr.2005.05.004
  26. Chowdhury D, Sen R: Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangements. Immunity 18;229-241, 2003 https://doi.org/10.1016/S1074-7613(03)00030-X
  27. Maki K, Sunaga S, Ikuta K: The V-J recombination of T cell receptor-gamma genes is blocked in interleukin-7 receptor- deficient mice. J Exp Med 184;2423-2427, 1996 https://doi.org/10.1084/jem.184.6.2423
  28. Meier D, Bornmann C, Chappaz S, Schmutz S, Otten LA, Ceredig R, Acha-Orbea H, Finke D: Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity 26;643-654, 2007 https://doi.org/10.1016/j.immuni.2007.04.009
  29. Chappaz S, Finke D: The IL-7 signaling pathway regulates lymph node development independent of peripheral lymphocytes. J Immunol 184;3562-3569, 2010 https://doi.org/10.4049/jimmunol.0901647
  30. Spits H, Di Santo JP: The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. Nat Immunol 12;21-27, 2011
  31. Park JH, Adoro S, Lucas PJ, Sarafova SD, Alag AS, Doan LL, Erman B, Liu X, Ellmeier W, Bosselut R, Feigenbaum L, Singer A: 'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR. Nat Immunol 8;1049-1059, 2007 https://doi.org/10.1038/ni1512
  32. Park JH, Yu Q, Erman B, Appelbaum JS, Montoya-Durango D, Grimes HL, Singer A: Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival. Immunity 21;289-302, 2004 https://doi.org/10.1016/j.immuni.2004.07.016
  33. Guimond M, Fry TJ, Mackall CL: Cytokine signals in T-cell homeostasis. J Immunother 28;289-294, 2005 https://doi.org/10.1097/01.cji.0000165356.03924.e7
  34. Namen AE, Lupton S, Hjerrild K, Wignall J, Mochizuki DY, Schmierer A, Mosley B, March CJ, Urdal D, Gillis S: Stimulation of B-cell progenitors by cloned murine interleukin- 7. Nature 333;571-573, 1988 https://doi.org/10.1038/333571a0
  35. Schmierer A, Mosley B, March CJ, Urdal D, Gillis S: Stimulation of B-cell progenitors by cloned murine interleukin- 7. Nature 333;571-573, 1988 https://doi.org/10.1038/333571a0
  36. Link A, Vogt TK, Favre S, Britschgi MR, Acha-Orbea H, Hinz B, Cyster JG, Luther SA: Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat Immunol 8;1255-1265, 2007 https://doi.org/10.1038/ni1513
  37. Watanabe M, Ueno Y, Yajima T, Iwao Y, Tsuchiya M, Ishikawa H, Aiso S, Hibi T, Ishii H: Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. J Clin Invest 95;2945-2953, 1995 https://doi.org/10.1172/JCI118002
  38. Golden-Mason L, Kelly AM, Traynor O, McEntee G, Kelly J, Hegarty JE, O'Farrelly C: Expression of interleukin 7 (IL-7) mRNA and protein in the normal adult human liver: implications for extrathymic T cell development. Cytokine 14;143-151, 2001 https://doi.org/10.1006/cyto.2001.0852
  39. Heufler C, Topar G, Grasseger A, Stanzl U, Koch F, Romani N, Namen AE, Schuler G: Interleukin 7 is produced by murine and human keratinocytes. J Exp Med 178;1109-1114, 1993 https://doi.org/10.1084/jem.178.3.1109
  40. Matsue H, Bergstresser PR, Takashima A: Keratinocyte-derived IL-7 serves as a growth factor for dendritic epidermal T cells in mice. J Immunol 151;6012-6019, 1993
  41. Cheng Y, Yata A, Klein C, Cho JH, Deguchi M, Hsueh AJ: Oocyte-Expressed Interleukin 7 Suppresses Granulosa Cell Apoptosis and Promotes Oocyte Maturation in Rats. Biol Reprod 2010 [Epub ahead of print]
  42. Moors M, Vudattu NK, Abel J, Krämer U, Rane L, Ulfig N, Ceccatelli S, Seyfert-Margolies V, Fritsche E, Maeurer MJ: Interleukin-7 (IL-7) and IL-7 splice variants affect differentiation of human neural progenitor cells. Genes Immun 11;11-20, 2010 https://doi.org/10.1038/gene.2009.77
  43. Di Carlo E, D'Antuono T, Pompa P, Giuliani R, Rosini S, Stuppia L, Musiani P, Sorrentino C: The lack of epithelial interleukin-7 and BAFF/BLyS gene expression in prostate cancer as a possible mechanism of tumor escape from immunosurveillance. Clin Cancer Res 15;2979-2987, 2009 https://doi.org/10.1158/1078-0432.CCR-08-1951
  44. Guimond M, Veenstra RG, Grindler DJ, Zhang H, Cui Y, Murphy RD, Kim SY, Na R, Hennighausen L, Kurtulus S, Erman B, Matzinger P, Merchant MS, Mackall CL: Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells. Nat Immunol 10;149-157, 2009 https://doi.org/10.1038/ni.1695
  45. Banwell CM, Partington KM, Jenkinson EJ, Anderson G: Studies on the role of IL-7 presentation by mesenchymal fibroblasts during early thymocyte development. Eur J Immunol 30;2125-2129, 2000 https://doi.org/10.1002/1521-4141(2000)30:8<2125::AID-IMMU2125>3.0.CO;2-H
  46. Lai L, Goldschneider I: Cutting edge: Identification of a hybrid cytokine consisting of IL-7 and the beta-chain of the hepatocyte growth factor/scatter factor. J Immunol 167; 3550-3554, 2001 https://doi.org/10.4049/jimmunol.167.7.3550
  47. Fry TJ, Mackall CL: The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance. J Immunol 174;6571-6576, 2005 https://doi.org/10.4049/jimmunol.174.11.6571
  48. Muthukumar A, Wozniakowski A, Gauduin MC, Paiardini M, McClure HM, Johnson RP, Silvestri G, Sodora DL: Elevated interleukin-7 levels not sufficient to maintain T-cell homeostasis during simian immunodeficiency virus-induced disease progression. Blood 103;973-979, 2004
  49. Napolitano LA, Grant RM, Deeks SG, Schmidt D, De Rosa SC, Herzenberg LA, Herndier BG, Andersson J, McCune JM: Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis. Nat Med 7;73-79, 2001 https://doi.org/10.1038/83381
  50. Sawa Y, Arima Y, Ogura H, Kitabayashi C, Jiang JJ, Fukushima T, Kamimura D, Hirano T, Murakami M: Hepatic interleukin-7 expression regulates T cell responses. Immunity 30;447-457, 2009 https://doi.org/10.1016/j.immuni.2009.01.007
  51. Alves NL, Richard-Le Goff O, Huntington ND, Sousa AP, Ribeiro VS, Bordack A, Vives FL, Peduto L, Chidgey A, Cumano A, Boyd R, Eberl G, Di Santo JP: Characterization of the thymic IL-7 niche in vivo. Proc Natl Acad Sci U S A 106;1512-1517, 2009 https://doi.org/10.1073/pnas.0809559106
  52. Repass JF, Laurent MN, Carter C, Reizis B, Bedford MT, Cardenas K, Narang P, Coles M, Richie ER: IL7-hCD25 and IL7-Cre BAC transgenic mouse lines: new tools for analysis of IL-7 expressing cells. Genesis 47;281-287, 2009 https://doi.org/10.1002/dvg.20497
  53. Mazzucchelli RI, Warming S, Lawrence SM, Ishii M, Abshari M, Washington AV, Feigenbaum L, Warner AC, Sims DJ, Li WQ, Hixon JA, Gray DH, Rich BE, Morrow M, Anver MR, Cherry J, Naf D, Sternberg LR, McVicar DW, Farr AG, Germain RN, Rogers K, Jenkins NA, Copeland NG, Durum SK: Visualization and identification of IL-7 producing cells in reporter mice. PLoS One 4;e7637, 2009 https://doi.org/10.1371/journal.pone.0007637
  54. Shalapour S, Deiser K, Sercan O, Tuckermann J, Minnich K, Willimsky G, Blankenstein T, Hämmerling GJ, Arnold B, Schüler T: Commensal microflora and interferon-gamma promote steady-state interleukin-7 production in vivo. Eur J Immunol 40;2391-2400, 2010 https://doi.org/10.1002/eji.201040441
  55. Soriano P: Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21;70-71, 1999 https://doi.org/10.1038/5007
  56. Srinivas S, Watanabe T, Lin CS, William CM, Tanabe Y, Jessell TM, Costantini F: Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev Biol 1;4, 2001 https://doi.org/10.1186/1471-213X-1-4
  57. Zamisch M, Moore-Scott B, Su DM, Lucas PJ, Manley N, Richie ER: Ontogeny and regulation of IL-7-expressing thymic epithelial cells. J Immunol 174;60-67, 2005 https://doi.org/10.4049/jimmunol.174.1.60
  58. Szymczak AL, Workman CJ, Wang Y, Vignali KM, Dilioglou S, Vanin EF, Vignali DA: Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptidebased retroviral vector. Nat Biotechnol 22;589-594, 2004 https://doi.org/10.1038/nbt957
  59. Fry TJ, Mackall CL: Interleukin-7: master regulator of peripheral T-cell homeostasis? Trends Immunol 22;564-571, 2001 https://doi.org/10.1016/S1471-4906(01)02028-2
  60. Alves NL, Huntington ND, Mention JJ, Richard-Le Goff O, Di Santo JP: Cutting Edge: a thymocyte-thymic epithelial cell cross-talk dynamically regulates intrathymic IL-7 expression in vivo. J Immunol 184;5949-5953, 2010 https://doi.org/10.4049/jimmunol.1000601
  61. Chappaz S, Flueck L, Farr AG, Rolink AG, Finke D: Increased TSLP availability restores T- and B-cell compartments in adult IL-7 deficient mice. Blood 110;3862-3870, 2007 https://doi.org/10.1182/blood-2007-02-074245
  62. Mazo IB, Honczarenko M, Leung H, Cavanagh LL, Bonasio R, Weninger W, Engelke K, Xia L, McEver RP, Koni PA, Silberstein LE, von Andrian UH: Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells. Immunity 22;259-270, 2005 https://doi.org/10.1016/j.immuni.2005.01.008
  63. Oshima S, Nakamura T, Namiki S, Okada E, Tsuchiya K, Okamoto R, Yamazaki M, Yokota T, Aida M, Yamaguchi Y, Kanai T, Handa H, Watanabe M: Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells. Mol Cell Biol 24;6298-6310, 2004 https://doi.org/10.1128/MCB.24.14.6298-6310.2004

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