Immune Regulatory Function of Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase in Orally Tolerance to Type II Collagen-induced Animal Model

제2형 콜라겐 경구관용 유도 동물모델에서 수지상 세포의 Indoleamine 2,3-dioxygenase의 의존성 관절염 항원 특이 T세포 증식반응 제어 연구

  • Park, Min-Jung (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Min, So-Youn (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Park, Kyoung-Su (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Cho, Mi-La (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • CHo, Young-Gyu (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Min, Jun-Ki (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Yoon, Chong-Hyeon (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Park, Sung-Hwa (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Kim, Ho-Youn (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea)
  • 박민정 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 민소연 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 박경수 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 조미라 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 조영규 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 민준기 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 윤종현 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 박성환 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 김호연 (가톨릭대학교 의과학연구원 류마티스연구센터)
  • Published : 2005.12.30

Abstract

Background: Immune regulatory dendritic cells (DCs) play an important role in maintaining self-tolerance. Recent evidences demonstrate that DCs expressing indoleamine 2,3-dioxygenase (IDO), which is involved in tryptophan catabolism, play an important role in immunoregulation and tolerance and induce T cell apoptosis. This study was devised to examine the role of IDO in the oral tolerance induction in collagen-induced arthritis (CIA) mouse model. Methods: Beginning 2 weeks before immunization, CII was fed six times to DBA/1 mice and the effect on arthritis was assessed. In tolerized mice, $CD11c^+$ DCs were isolated and stimulated with CII, IFN-${\gamma}$, and LPS with or without IDO inhibitor, 1-methyl-DL-tryptophan (1-MT) and IDO expression by $CD11c^+$ DCs was analyzed using FACS and RT-PCR. The expression of IDO, MHC II, CD80, and CD86 by $CD11c^+$ DCs were examined using confocal microscopy. Regulatory effect of $CD11c^+$ DCs on Ag-specific T cell proliferative response to CII was examined by mixed lymphocyte reaction (MLR) with or without 1-MT. Results: The proportion of IDO-expressing $CD11c^+$ DCs was slightly higher in tolerized mice than in CIA mice and significantly increased after stimulation with CII, IFN-${\gamma}$, and LPS in an IDO-dependent manner. On confocal microscopic examination, the expression of IDO was higher and those of MHC II and CD86 were lower in CD11c + DCs from tolerized mice compared to those from CIA mice. On MLR, $CD11c^+$ DCs from tolerized mice inhibited T cell proliferative response to CII in an IDO-dependent manner. Conclusion: Enhanced IDO expression by $CD11c^+$ DCs from tolerized mice may contribute to the regulation of proliferative response of CII-reactive T cells and could be involved in the induction of oral tolerance to CII.

Keywords

References

  1. Nagler-Anderson C, Bober LA, Robinson ME, Siskind GW, Thorbecke GJ: Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen. Proc Natl Acad Sci USA 83;7443-7446, 1986
  2. Garcia G, Komagata Y, Slavin AJ, Maron R, Weiner HL: Suppression of collagen-induced arthritis by oral or nasal administration of type II collagen. J Autoimmun 13;315-324, 1999 https://doi.org/10.1006/jaut.1999.0320
  3. Fishman-Lobell J, Friedman A, Weiner HL: Different kinetic patterns of cytokine gene expression in vivo in orally tolerant mice. Eur J Immunol 24;2720-2724, 1994 https://doi.org/10.1002/eji.1830241122
  4. Tsuji NM, Mizumachi K, Kurisaki J: Interleukin-10-secreting Peyer's patch cells are responsible for active suppression in low-dose oral tolerance. Immunology 103;458-464, 2001 https://doi.org/10.1046/j.1365-2567.2001.01265.x
  5. Friedman A, Weiner HL: Induction of anergy or active suppression following oral tolerance is determined by antigen dosage. Proc Natl Acad Sci USA 91;6688-6692, 1994
  6. Steinman RM, Nussenzweig MC: Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci USA 99;351-358, 2002
  7. Wakkach A, Fournier N, Brun V, Breittmayer JP, Cottrez F, Groux H: Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18;605-617, 2003 https://doi.org/10.1016/S1074-7613(03)00113-4
  8. Derry CJ, Harper N, Davies DH, Murphy JJ, Staines NA: Importance of dose of type II collagen in suppression of collagen-induced arthritis by nasal tolerance. Arthritis Rheum 44;1917-1927, 2001 https://doi.org/10.1002/1529-0131(200108)44:8<1917::AID-ART330>3.0.CO;2-W
  9. Daniels LK: Rapid in-office and in-vivo desensitization of an injection phobia utilizing hypnosis. Am J Clin Hypn 18;200-203, 1976 https://doi.org/10.1080/00029157.1976.10403798
  10. Mowat AM, Parker LA, Beacock-Sharp H, Millington OR, Chirdo F: Oral tolerance: overview and historical perspectives. Ann N Y Acad Sci 1029;1-8, 2004 https://doi.org/10.1196/annals.1309.001
  11. Dubois B, Goubier A, Joubert G, Kaiserlian D: Oral tolerance and regulation of mucosal immunity. Cell Mol Life Sci 62;1322-1332, 2005 https://doi.org/10.1007/s00018-005-5036-0
  12. Kelsall BL, Leon F: Involvement of intestinal dendritic cells in oral tolerance, immunity to pathogens, and inflammatory bowel disease. Immunol Rev 206;132-148, 2005 https://doi.org/10.1111/j.0105-2896.2005.00292.x
  13. Yoshida R, Nukiwa T, Watanabe Y, Fujiwara M, Hirata F, Hayaishi O: Regulation of indoleamine 2,3-dioxygenase activity in the small intestine and the epididymis of mice. Arch Biochem Biophys 203;343-351. 1980 https://doi.org/10.1016/0003-9861(80)90185-X
  14. Yoshida R, Urade Y, Nakata K, Watanabe Y, Hayaishi O: Specific induction of indoleamine 2,3-dioxygenase by bacterial lipopolysaccharide in the mouse lung. Arch Biochem Biophys 212;629-637, 1981 https://doi.org/10.1016/0003-9861(81)90406-9
  15. Malina HZ, Martin XD: Indoleamine 2,3-dioxygenase: antioxidant enzyme in the human eye. Graefes Arch Clin Exp Ophthalmol 234;457-462, 1996 https://doi.org/10.1007/BF02539413
  16. Moffett JR, Espey MG, Namboodiri MA: Antibodies to quinolinic acid and the determination of its cellular distribution within the rat immune system. Cell Tissue Res 278;461-469, 1994 https://doi.org/10.1007/BF00331364
  17. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ: Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 9;1269-1274, 2003 https://doi.org/10.1038/nm934
  18. Lee JR, Dalton RR, Messina JL, Sharma MD, Smith DM, Burgess RE, Mazzella F, Antonia SJ, Mellor AL, Munn DH: Pattern of recruitment of immunoregulatory antigen-presenting cells in malignant melanoma. Lab Invest 83;1457-1466, 2003 https://doi.org/10.1097/01.LAB.0000090158.68852.D1
  19. Taylor MW, Feng GS: Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. Faseb J 5;2516-2522, 1991
  20. Pfefferkorn ER: Interferon gamma blocks the growth of toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. Proc Natl Acad Sci USA 81;908-912, 1984
  21. Gupta SL, Carlin JM, Pyati P, Dai W, Pfefferkorn ER, Murphy MJ Jr: Antiparasitic and antiproliferative effects of indoleamine 2,3-dioxygenase enzyme expression in human fibroblasts. Infect Immun 62;2277-2284, 1994
  22. Mellor AL, Munn DH: Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today 20;469-473, 1999 https://doi.org/10.1016/S0167-5699(99)01520-0
  23. Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL: Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 189;1363-1372, 1999 https://doi.org/10.1084/jem.189.9.1363
  24. Hwu P, Du MX, Lapointe R, Do M, Taylor MW, Young HA: Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J Immunol 164;3596-3599, 2000 https://doi.org/10.4049/jimmunol.164.7.3596
  25. Xiao BG, Liu X, Link H: Antigen-specific T cell functions are suppressed over the estrogen-dendritic cell-indoleamine 2,3-dioxygenase axis. Steroids 69;653-659, 2004 https://doi.org/10.1016/j.steroids.2004.05.019
  26. Mellor AL, Sivakumar J, Chandler P, Smith K, Molina H, Mao D, Munn DH: Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol 2;64-68, 2001 https://doi.org/10.1038/83183
  27. Hwang SL, Chung NP, Chan JK, Lin CL: Indoleamine 2,3-dioxygenase (IDO) is essential for dendritic cell activation and chemotactic responsiveness to chemokines. Cell Res 15;167-175, 2005 https://doi.org/10.1038/sj.cr.7290282
  28. Trentham DE, Townes AS, Kang AH: Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med 146;857-868, 1977 https://doi.org/10.1084/jem.146.3.857
  29. Piccirillo CA, Letterio JJ, Thornton AM, McHugh RS, Mamura M, Mizuhara H, Shevach EM: CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J Exp Med 196;237-246, 2002 https://doi.org/10.1084/jem.20020590
  30. Hirofuji T, Kakimoto K, Hori H, Nagai Y, Saisho K, Sumiyoshi A, Koga T: Characterization of monoclonal antibody specific for human type II collagen: possible implication in collagen-induced arthritis. Clin Exp Immunol 62;159-166, 1985
  31. Bozza S, Fallarino F, Pitzurra L, Zelante T, Montagnoli C, Bellocchio S, Mosci P, Vacca C, Puccetti P, Romani L: A crucial role for tryptophan catabolism at the host/Candida albicans interface. J Immunol 174;2910-2918, 2005 https://doi.org/10.4049/jimmunol.174.5.2910
  32. Alexander AM, Crawford M, Bertera S, Rudert WA, Takikawa O, Robbins PD, Trucco M: Indoleamine 2,3-dioxygenase expression in transplanted NOD Islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes. Diabetes 51;356-365, 2002 https://doi.org/10.2337/diabetes.51.2.356
  33. Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr, Mellor AL: Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297;1867-1870, 2002 https://doi.org/10.1126/science.1073514
  34. Tan PH, Beutelspacher SC, Wang YH, McClure MO, Ritter MA, Lombardi G, George AJ: Immunolipoplexes: an efficient, nonviral alternative for transfection of human dendritic cells with potential for clinical vaccination. Mol Ther 11;790-800, 2005 https://doi.org/10.1016/j.ymthe.2004.12.009
  35. Grohmann U, Fallarino F, Puccetti P: Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol 24;242-248, 2003 https://doi.org/10.1016/S1471-4906(03)00072-3
  36. Mellor AL, Munn DH: Tryptophan catabolism and regulation of adaptive immunity. J Immunol 170;5809-5813, 2003 https://doi.org/10.4049/jimmunol.170.12.5809
  37. Terness P, Chuang JJ, Bauer T, Jiga L, Opelz G: Regulation of human auto- and alloreactive T cells by indoleamine 2,3-dioxygenase (IDO)-producing dendritic cells: too much ado about IDO? Blood 105;2480-2486, 2005 https://doi.org/10.1182/blood-2004-06-2103