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Autoimmune Regulator Gene (Aire) is Expressed in Lymph Node Fibroblastic Reticular Cell, BLS4

Autoimmune regulator gene (Aire)의 마우스 림프절 FRC세포, BLS4에서 발현

  • Moon, Kyoung-Mi (Department of Biomaterial Control, Dong-Eui University) ;
  • Seo, Hee-Ju (Department of Biotechnology and Bioengineering, Dong-Eui University) ;
  • Oh, Ji-Youn (Department of Biotechnology and Bioengineering, Dong-Eui University) ;
  • Lee, Jae-Seol (Department of Biotechnology and Bioengineering, Dong-Eui University) ;
  • Kim, Hae-Young (Department of Biotechnology and Bioengineering, Dong-Eui University) ;
  • Kim, Jeong-Hwan (Department of Biomaterial Control, Dong-Eui University) ;
  • Choi, Woo-Bong (Department of Biomaterial Control, Dong-Eui University) ;
  • Kim, Byung-Woo (Department of Control Blue-Bio Regional Innovation Center, Dong-Eui University) ;
  • Kim, Kwang-Hyeon (Department of Life Science and Biotechnology, Dong-Eui University) ;
  • Lee, Jong-Hwan (Department of Biomaterial Control, Dong-Eui University)
  • 문경미 (동의대학교 바이오물질제어학과) ;
  • 서희주 (동의대학교 생명공학과) ;
  • 오지윤 (동의대학교 생명공학과) ;
  • 이재설 (동의대학교 생명공학과) ;
  • 김해영 (동의대학교 생명공학과) ;
  • 김정환 (동의대학교 바이오물질제어학과) ;
  • 최우봉 (동의대학교 바이오물질제어학과) ;
  • 김병우 (동의대학교 블루바이오 RIC) ;
  • 김광현 (동의대학교 생명응용학과) ;
  • 이종환 (동의대학교 바이오물질제어학과)
  • Received : 2010.03.11
  • Accepted : 2010.05.24
  • Published : 2010.05.31

Abstract

Autoimmune regulator gene (Aire) is expressed in the thymus and controls the expression of peripheral self-antigens, known as promiscuous genes. Aire and promiscuous genes are involved in T cell tolerance and autoimmunity in the thymus. Here, we identified Aire-expressing fibroblastic reticular cell (FRC), which was derived from mouse lymph node and also expressed in insulin promiscuous antigen. The expression of insulin was increased in cultured FRC over-expressed with Aire. These data suggest that Aire regulates promiscuous gene expression in FRC, and that this function might be under peripheral selection control.

Autoimmune regulator gene (Aire)는 흉선에서 발현되며 promiscuous genes으로 알려진 흉선에서 자가항원 발현을 조절한다. Aire 와 promiscuous genes은 흉선에서 T세포 tolerance와 자가면역에 관여한다. 말초 조직 즉 림프절에서 Aire의 역할을 알아보고자 림프절 구성 세포중 하나인 fibroblastic reticular cell (FRC)을 분리 확립하였다. 마우스 림프절로부터 분리된 FRC에서 Aire의 발현을 확인하였고 또한 promiscuous antigen인 insulin의 발현도 확인하였다. Aire 과발현 플라스미드로 형질전환 후 배양 FRC에서 Insulin의 발현이 증가하였다. 이것은 Aire가 FRC에서 promiscuous gene의 발현을 조절한다는 것을 보여주며 peripheral selection과 연관되어 있을 수 있다는 것을 제시한다.

Keywords

References

  1. Anderson, M. S, E. S., Venanzi, L. Klein, Z. Chen, S. P.Berzins, S. J. Turley, H. von Boehmer, R. Bronson, A.Dierich, C. Benoist, and D. Mathis. 2002. Projection of animmunological self shadow within the thymus by the aireprotein. Science 298, 1348-1349. https://doi.org/10.1126/science.1079323
  2. Bajenoff, M., J. G. Egen, L. Y. Koo, J. P. Laugier, F. Brau,N. Glaichenhaus, and R. N. Germain. 2006. Stromal cell networksregulate lymphocyte entry, migration, and territorialityin lymph nodes. Immunity 25, 989-1001. https://doi.org/10.1016/j.immuni.2006.10.011
  3. Bjorses, P., M. Pelto-Huikko, J. Kaukonen, J. Aaltonen, L.Peltonen, and I. Ulmanen. 1999. Localization of theAPECED protein in distinct nuclear structures. Hum. Mol. Genet. 8, 259-266. https://doi.org/10.1093/hmg/8.2.259
  4. Chen, J., W. Yang, C. Yu, and Y. Li. 2008. Autoimmuneregulator initiates the expression of promiscuous genes inthymic epithelial cells. Immunol. Invest. 37, 203-214. https://doi.org/10.1080/08820130801967841
  5. Gardner, J. M., J. J. Devoss, R. S. Friedman, D. J. Wong,Y. X. Tan, X. Zhou, K. P. Johannes, M. A. Su, H. Y. Chang,M. F. Krummel, and M. S. Anderson. 2008. Deletional tolerancemediated by extrathymic Aire-expressing cells. Science321, 843-847. https://doi.org/10.1126/science.1159407
  6. Gardner, J. M., A. L. Fletcher, M. S. Anderson, and S. J.Turley. 2009. AIRE in the thymus and beyond. Curr. Opin. Immunol. 21, 582-589. https://doi.org/10.1016/j.coi.2009.08.007
  7. Hara, T., T. Katakai, J. H. Lee, Y. Nambu, N.Nakajima-Nagata, H. Gonda, M. Sugai, and A. Shimizu.2006. A transmembrane chemokine, CXC chemokine ligand16, expressed by lymph node fibroblastic reticular cells hasthe potential to regulate T cell migration and adhesion. Int. Immunol. 18, 301-311. https://doi.org/10.1093/intimm/dxh369
  8. Heino, M., P. Peterson, J. Kudoh, K. Nagamine, A.Lagerstedt, V. Ovod, A. Ranki, I. Rantala, M. Nieminen, J.Tuukkanen, H. S. Scott, S. E. Antonarakis, N. Shimizu, andK. Krohn. 1999. Autoimmune regulator is expressed in thecells regulating immune tolerance in thymus medulla.Biochem. Biophys. Res. Commun. 257, 821-825. https://doi.org/10.1006/bbrc.1999.0308
  9. Heino, M., P. Peterson, N. Sillanpaa, S. Guerin, L. Wu, G.Anderson, H. S. Scott, S. E. Antonarakis, J. Kudoh, N.Shimizu, E. J. Jenkinson, P. Naquet, and K. J. Krohn. 2000.RNA and protein expression of the murine autoimmuneregulator gene (Aire) in normal, RelB-deficient and in NOD mouse. Eur. J. Immunol. 30, 1884-1893. https://doi.org/10.1002/1521-4141(200007)30:7<1884::AID-IMMU1884>3.0.CO;2-P
  10. Katakai, T., T. Hara, M. Sugai, H. Gonda, and A. Shimizu.2004. Lymph node fibroblastic reticular cells construct thestromal reticulum via contact with lymphocytes. J. Exp. Med.200, 783-795. https://doi.org/10.1084/jem.20040254
  11. Kogawa, K., S. Nagafuchi, H. Katsuta, J. Kudoh, S. Tamiya,Y. Sakai, N. Shimizu, and M. Harada. 2002. Expression ofAIRE gene in peripheral monocyte/dendritic cell lineage.Immunol. Lett. 80, 195-198. https://doi.org/10.1016/S0165-2478(01)00314-5
  12. Kont, V., M. Laan, K. Kisand, A. Merits, H. S. Scott, andP. Peterson. 2008. Modulation of Aire regulates the expressionof tissue-restricted antigens. Mol. Immunol. 45,25-33. https://doi.org/10.1016/j.molimm.2007.05.014
  13. Lee, J. W., M. Epardaud, J. Sun, J. E. Becker, A. C. Cheng,A. R. Yonekura, J. K. Heath, and S. J. Turley. 2007.Peripheral antigen display by lymph node stroma promotesT cell tolerance to intestinal self. Nat. Immunol. 8, 181-190. https://doi.org/10.1038/ni1427
  14. Liston, A., S. Lesage, J. Wilson, L. Peltonen, and C. C.Goodnow. 2003. Aire regulates negative selection of organ-specific T cells. Nat. Immunol. 4, 350-354. https://doi.org/10.1038/ni906
  15. Mittaz, L., C. Rossier, M. Heino, P. Peterson, K. J. Krohn,Gos A, M. A. Morris, J. Kudoh, N. Shimizu, S. E.Antonarakis, and H. S. Scott.1999. Isolation and characterization of the mouse Aire gene. Biochem. Biophys. Res. Commun. 255, 483-490. https://doi.org/10.1006/bbrc.1999.0223
  16. Nagamine, K., P. Peterson, H. S. Scott, J. Kudoh, S.Minoshima, M. Heino, K. J. Krohn, M. D. Lalioti, P. E.Mullis, S. E. Antonarakis, K. Kawasaki, S. Asakawa, F. Ito,and N. Shimizu.1997. Positional cloning of the APECEDgene. Nat. Genet. 17, 393-398. https://doi.org/10.1038/ng1297-393
  17. Poliani, P. L., K. Kisand, V. Marrella, M. Ravanini, L. D.Notarangelo, A. Villa, P. Peterson, and F. Facchetti. 2010.Human Peripheral Lymphoid Tissues Contain AutoimmuneRegulator-Expressing Dendritic Cells. Am. J. Pathol. [Epubahead of print]
  18. Ruan, Q. G., K. Tung, D. Eisenman, Y. Setiady, S.Eckenrode, B. Yi. S. Purohit, W. P. Zheng, Y. Zhang, L.Peltonen, and J. X. She. 2007. The autoimmune regulatordirectly controls the expression of genes critical for thymicepithelial function. J. Immunol. 178, 7173-7180. https://doi.org/10.4049/jimmunol.178.11.7173
  19. Xiao, W. 2004. Advances in NF-$\kappa$B signaling transductionand transcription. Cell Mol. Immunol. 1, 425-435.
  20. Zhu, M., R. K. Chin, P. A. Christiansen, J. C. Lo, X. Liu,C. Ware, U. Siebenlist, Y. X. Fu. 2006. NF-$\kappa$B2 is requiredfor the establishment of central tolerance through anAire-dependent pathway. J. Clin. Invest. 116, 2964-2971. https://doi.org/10.1172/JCI28326

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