IMMUNE NETWORK

  • 제5권1호
  • /
  • Pages.16-22
  • /
  • 2005
  • /
  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
권호 표지

Th2 세포에서 IL-12에 의한 IL-18R ${\alpha}$의 발현유지 및 IL-18 자극에 의한 GATA-3의 유도

IL-18R ${\alpha}$ Mediated GATA-3 Induction by Th2 Cells: IL-12 Supports IL-18R ${\alpha}$ Expression in Th2 Cells

  • 주인숙 (경희대학교 의과대학 미생물학교실) ;
  • 선민정 (경희대학교 의과대학 미생물학교실) ;
  • 김동영 (경희대학교 의과대학 미생물학교실) ;
  • 이수진 (경희대학교 의과대학 미생물학교실) ;
  • 하윤문 (경희대학교 의과대학 미생물학교실) ;
  • 조정제 (경희대학교 의과대학 미생물학교실) ;
  • 박증석 (경희대학교 의과대학 미생물학교실) ;
  • 안현종 (경희대학교 의과대학 미생물학교실)
  • Joo, In-Sook (Department of Microbiology, Kyung-Hee University Medical School) ;
  • Sun, Min-Jung (Department of Microbiology, Kyung-Hee University Medical School) ;
  • Kim, Dong-Young (Department of Microbiology, Kyung-Hee University Medical School) ;
  • Lee, Su-Jin (Department of Microbiology, Kyung-Hee University Medical School) ;
  • Ha, Youn-Mun (Department of Microbiology, Kyung-Hee University Medical School) ;
  • Cho, Jeong-Je (Department of Microbiology, Kyung-Hee University Medical School) ;
  • Park, Cheung-Seog (Department of Microbiology, Kyung-Hee University Medical School) ;
  • Ahn, Hyun-Jong (Department of Microbiology, Kyung-Hee University Medical School)
  • 발행 : 2005.03.31
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초록

Background: IL-18 was originally cloned as a IFN-${\gamma}$ inducing factor in primed T cells. In synergy with IL-12, IL-18 has been shown to induce strikingly high levels of IFN-${\gamma}$ production by T cells and to enhance Th1 development. Also this cytokine exerts induction of Th2 development through IL-4 induction. Methods: Resting $CD4^+$ T cells were sorted by negative selection and activated by anti-CD3 plus anti-CD28 Ab. Expression of IL-12 binding sites, IL-18 binding sites, IL-18R ${\alpha}$, and GATA-3 mRNA were analysed by FACS and RT-PCR, respectively. Results: Resting $CD4^+$ T cells expressed IL-18R ${\alpha}$ chain but not IL-18 binding sites, suggesting a lack of IL-18R ${\beta}$ expression. IL-18R ${\alpha}$ was maintained on the Th1 and Th2 committed cells. IL-18 binding sites were induced on the Th1 but not Th2 cells. Exposure of these cells to IL-18 led to up-regulation of GATA-3 mRNA expression only in Th2 committed cells. To elucidate the relationship between IL-18R ${\alpha}$ expression and GATA-3 induction by IL-18, Th1 and Th2 committed cells were further cultured in medium with or without IL-12 for 2 days. IL-12 binding sites were maintained on the Th1 and Th2 cells regardless of IL-12 treatment, but IL-18R a expression was rapidly down-regulated on the IL12-untreated Th2 cells which did not induce GATA-3 mRNA expression followed by IL-18 stimulation. Conclusion: IL-12 supports expression of IL-18R ${\alpha}$ and GATA-3 mRNA expression was induced by IL-18 through IL-18R ${\alpha}$ without expression of IL-18 binding site in Th2 cells.

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참고문헌

  1. Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K, Akita K, Namba M, Tanabe F, Konishi K, Fukuda S, Kurimoto M: Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378;88-91, 1995 https://doi.org/10.1038/378088a0
  2. Gu Y, Kuida K, Tsutsui H, Ku G, Hsiao K, Fleming MA, Hayashi N, Higashino K, Okamura H, Nakanishi K, Kurimoto M, Tanimoto T, Flavell RA, Sato V, Harding MW, Livingston DJ, Su MS: Activation of interferon-gamma inducing factor mediated by interleukin-1 beta converting enzyme. Science 275;206-209, 1997 https://doi.org/10.1126/science.275.5297.206
  3. Okamura H, Tsutsui H, Kashiwamura S, Yoshimoto T, Nakanishi K: Interleukin-18: a novel cytokine that augments both innate and acquired immunity. Adv Immunol 70;281312, 1998
  4. Xu D, Chan WL, Leung BP, Hunter D, Schulz K, Carter RW, McInnes IB, Robinson JH, Liew FY: Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells. J Exp Med 188;1485-1492, 1998 https://doi.org/10.1084/jem.188.8.1485
  5. Ahn HJ, Maruo S, Tomura M, Mu J, Hamaoka T, Nakanishi K, Clark S, Kurimoto M, Okamura H, Fujiwara H: A mechanism underlying synergy between IL-12 and IFN-gamma inducing factor in enhanced production of IFN-gamma. J Immunol 159;2125-2131, 1997
  6. Nakahira M, Ahn HJ, Park WR, Gao P, Tomura M, Park CS, Hamaoka T, Ohta T, Kurimoto M, Fujiwara H: Synergy of IL-12 and IL-18 for IFN-gamma gene expression: IL-12 induced STAT4 contributes to IFN-gamma promoter activation by up regulating the binding activity of IL-18 induced activator protein 1. J Immunol 168; 1146-1153, 2002 https://doi.org/10.4049/jimmunol.168.3.1146
  7. Takeda K, Tsutsui H, Yoshimoto T, Adachi O, Yoshida N, Kishimoto T, Okamura H, Nakanishi K, Akira S: Defective NK cell activity and Th1 response in IL-18 deficient mice. Immunity 8;383-390, 1998 https://doi.org/10.1016/S1074-7613(00)80543-9
  8. Robinson D, Shibuya K, Mui A, Zonin F, Murphy E, Sana T, Hartley SB, Menon S, Kastelein R, Bazan F, O'Garra A: IGIF does not drive Thl development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NF-kappaB. Immunity 7;571-581, 1997 https://doi.org/10.1016/S1074-7613(00)80378-7
  9. Guler ML, Gorham JD, Hsieh CS, Mackey AJ, Steen RG, Dietrich WF, Murphy KM: Genetic susceptibility to Leishmania: IL-12 responsiveness in TH1 cell development. Science 271;984-987, 1996 https://doi.org/10.1126/science.271.5251.984
  10. Kaplan MH, Sun YL, Hoey T, Grusby MJ: Impaired IL-12 responses and enhanced development of Th2 cells in Stat4 deficient mice. Nature 382;174-177, 1996 https://doi.org/10.1038/382174a0
  11. Rogge L, Barberis Maino L, Biffi M, Passini N, Presky DH, Gubler U, Sinigaglia F: Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J Exp Med 185;825-831, 1997 https://doi.org/10.1084/jem.185.5.825
  12. Szabo SJ, Dighe AS, Gubler U, Murphy KM: Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med 185;817824, 1997
  13. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH: A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100;655-669, 2000 https://doi.org/10.1016/S0092-8674(00)80702-3
  14. Mullen AC, High FA, Hutchins AS, Lee HW, Villarino AV, Livingston DM, Kung AL, Cereb N, Yao TP, Yang SY, Reiner SL: Role of T-bet in comtnitment of TH1 cells before IL-12 dependent selection. Science 292;1907-1910, 2001 https://doi.org/10.1126/science.1059835
  15. Finotto S, Neurath MF, Glickman IN, Qin S, Lehr HA, Green FH, Ackerman K, Haley K, Galle PR, Szabo SJ, Drazen JM, De Sanctis GT, Glimcher LH: Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295;336-338, 2002 https://doi.org/10.1126/science.1065544
  16. Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N, Yang SY, Murphy TL, Murphy KM: T bet is a STATI induced regulator of IL-12R expression in naive $CD4^+$ T cells. Nat Immunol 3;549-557, 2002 https://doi.org/10.1038/ni794
  17. Yoshimoto T, Mizutani H, Tsutsui H, Noben Trauth N, Yamanaka K, Tanaka M, Izumi S, Okamura H, Paul WE, Nakanishi K: IL-18 induction of IgE: dependence on $CD4^+$ T cells, IL-4 and STAT6. Nat Immunol 1;132-137, 2000 https://doi.org/10.1038/77811
  18. Ouyang W, Lohning M, Gao Z, Assenmacher M, Ranganath S, Radbruch A, Murphy KM: Stat6 independent GATA-3 autoactivation directs IL-4 independent Th2 development and comtnitment. Immunity 12;27-37, 2000 https://doi.org/10.1016/S1074-7613(00)80156-9
  19. Murphy KM, Ouyang W, Farrar JD, Yang J, Ranganath S, Asnagli H, Afkarian M, Murphy TL: Signaling and transcription in T helper development. Annu Rev Immunol 18; 451-494, 2000 https://doi.org/10.1146/annurev.immunol.18.1.451
  20. Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H: Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 19;423-474, 2001 https://doi.org/10.1146/annurev.immunol.19.1.423
  21. Wysocka M, Kubin M, Vieira LQ, Ozmen L, Garotta G, Scott P, Trinchieri G: Interleukin-12 is required for interferon lipopolysaccharide Eur J Immunol 25;672-676, 1995 https://doi.org/10.1002/eji.1830250307
  22. Ozato K, Mayer NM, Sachs DB: Monoclonal antibodies to mouse major histocompatibility complex antigens. Transplantation 34;113-120, 1982 https://doi.org/10.1097/00007890-198209000-00001
  23. Leo O, Foo M, Sachs DH, Samelson LE, Bluestone JA: Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci USA 84;1374-1378, 1987
  24. Abe R, Vandenberghe P, Craighead N, Smoot DS, Lee KP, June CH; Distinct signal transduction in mouse CD4+ and CD8+ splenic T cells after CD28 receptor ligation. J Immunol 154;985-997, 1995
  25. Born TL, Thomassen E, Bird TA, Sims JE: Cloning of a novel receptor subunit, AcPL, required for interleukin-18 signaling. J Biol Chem 273;29445-29450, 1998 https://doi.org/10.1074/jbc.273.45.29445
  26. O'Neill LA, Greene C: Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants. J Leukoc Biol 63;650-657, 1998 https://doi.org/10.1002/jlb.63.6.650
  27. Wu C, Sakorafas P, Miller R, McCarthy D, Scesney S, Dixon R, Ghayur T: IL-18 receptor beta induced changes in the presentation of IL-18 binding sites affect ligand binding and signal transduction. J Immunol 170;5571-5577, 2003 https://doi.org/10.4049/jimmunol.170.11.5571
  28. Yoshimoto T, Takeda K, Tanaka T, Ohkusu K, Kashiwamura S, Okamura H, Akira S, Nakanishi K: IL-12 up regulates IL18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production. J Immunol 161;3400-3407, 1998
  29. Sareneva T, Julkunen I, Matikainen S: IFN-alpha and IL-12 induce IL-18 receptor gene expression in human NK and T cells. J Immunol 165;1933-1938, 2000 https://doi.org/10.4049/jimmunol.165.4.1933
  30. Lawless VA, Zhang S, Ozes ON, Bruns HA, Oldham I, Hoey T, Grusby MJ, Kaplan MH: Stat4 regulates multiple components of IFN-gamma inducing signaling pathways. J Immunol 165;6803-6808, 2000 https://doi.org/10.4049/jimmunol.165.12.6803
  31. Kim SH, Reznikov LL, Stuyt RJ, Selzman CH, Fantuzzi G, Hoshino T, Young HA, Dinarello CA: Functional reconstitution and regulation of IL-18 activity by the IL 18R beta chain. J Immunol 166;148-154, 2001 https://doi.org/10.4049/jimmunol.166.1.148
  32. Bluestone JA, Pardoll D, Sharrow SO, Fowlkes BJ: Characterization of murine thymocytes with CD3 associated T cell receptor structures. Nature 326;82-84, 1987 https://doi.org/10.1038/326082a0
  33. Kaliyaperumal A, Falchetto R, Cox A, Dick R 2nd, Shabanowitz J, Chien YH, Matis L, Hunt DF, Bluestone JA: Functional expression and recognition of nonclassical MHC class I TI0b is not peptide dependent. J Immunol 155;2379-2386, 1995
  34. Lewis DB: Allergy immunotherapy and inhibition of Th2 immune responses: a sufficient strategy? Curr Opin Immunol 14;644-651, 2002 https://doi.org/10.1016/S0952-7915(02)00388-6
  35. Torigoe K, Ushio S, Okura T, Kobayashi S, Taniai M, Kunikata T, Murakami T, Sanou O, Kojima H, Fujii M, Ohta T, Ikeda M, Ikegami H, Kurimoto M: Purification and characterization of the human interleukin. Biol Chem 272;25737-25742, 1997 https://doi.org/10.1074/jbc.272.41.25737
  36. Nakahira M, Tomura M, Iwasaki M, Ahn HJ, Bian Y, Hamaoka T, Ohta T, Kurimoto M, Fujiwara H: An absolute requirement for STAT4 and a role for IFN-gamma as an amplifying factor in IL-12 induction of the functional IL-18 receptor complex. J Immunol 167;1306-1312, 2001 https://doi.org/10.4049/jimmunol.167.3.1306