IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

TCF4-Targeting miR-124 is Differentially Expressed amongst Dendritic Cell Subsets

  • Sun Murray Han (Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine) ;
  • Hye Young Na (Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine) ;
  • Onju Ham (Brain Korea 21 PLUS Project for Medical Science, Severance Biomedical Science Institute, Yonsei University College of Medicine) ;
  • Wanho Choi (Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine) ;
  • Moah Sohn (Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine) ;
  • Seul Hye Ryu (Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine) ;
  • Hyunju In (Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine) ;
  • Ki-Chul Hwang (Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University) ;
  • Chae Gyu Park (Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine)
  • Received : 2015.11.10
  • Accepted : 2016.01.15
  • Published : 2016.02.29
Download PDF
⟨ Previous Next ⟩

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells that sample their environment and present antigens to naïve T lymphocytes for the subsequent antigen-specific immune responses. DCs exist in a range of distinct subpopulations including plasmacytoid DCs (pDCs) and classical DCs (cDCs), with the latter consisting of the cDC1 and cDC2 lineages. Although the roles of DC-specific transcription factors across the DC subsets have become understood, the posttranscriptional mechanisms that regulate DC development are yet to be elucidated. MicroRNAs (miRNAs) are pivotal posttranscriptional regulators of gene expression in a myriad of biological processes, but their contribution to the immune system is just beginning to surface. In this study, our in-house probe collection was screened to identify miRNAs possibly involved in DC development and function by targeting the transcripts of relevant mouse transcription factors. Examination of DC subsets from the culture of mouse bone marrow with Flt3 ligand identified high expression of miR-124 which was able to target the transcript of TCF4, a transcription factor critical for the development and homeostasis of pDCs. Further expression profiling of mouse DC subsets isolated from in vitro culture as well as via ex vivo purification demonstrated that miR-124 was outstandingly expressed in CD24+ cDC1 cells compared to in pDCs and CD172α+ cDC2 cells. These results imply that miR-124 is likely involved in the processes of DC subset development by posttranscriptional regulation of a transcription factor(s).

Keywords

Acknowledgement

We thank Young Hee Nam for her help with flow cytometry at the Flow Cytometry Core of the Yonsei Biomedical Research Institute in the Yonsei University College of Medicine. We were supported by grants from the National Research Foundation of Korea (NRF2013R1A1A2058427, NRF-2014R1A4A1008625) and a faculty research grant of Yonsei University College of Medicine for 2014 (6-2014-0062) to CGP, and the Brain Korea 21 PLUS Project for Medical Science, Yonsei University.

References

  1. Steinman, R. M. 2012. Decisions about dendritic cells: past, present, and future. Annu. Rev. Immunol. 30: 1-22. https://doi.org/10.1146/annurev-immunol-100311-102839
  2. Park, C. G. 2014. Vaccine strategies utilizing C-type lectin receptors on dendritic cells in vivo. Clin. Exp. Vaccine Res. 3: 149-154. https://doi.org/10.7774/cevr.2014.3.2.149
  3. Steinman, R. M., and J. Idoyaga. 2010. Features of the dendritic cell lineage. Immunol. Rev. 234: 5-17. https://doi.org/10.1111/j.0105-2896.2009.00888.x
  4. Kingston, D., M. A. Schmid, N. Onai, A. Obata-Onai, D. Baumjohann, and M. G. Manz. 2009. The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis. Blood 114: 835-843.
  5. Onai, N., K. Kurabayashi, M. Hosoi-Amaike, N. Toyama-Sorimachi, K. Matsushima, K. Inaba, and T. Ohteki. 2013. A clonogenic progenitor with prominent plasmacytoid dendritic cell developmental potential. Immunity 38: 943-957. https://doi.org/10.1016/j.immuni.2013.04.006
  6. Grajales-Reyes, G. E., A. Iwata, J. Albring, X. Wu, R. Tussiwand, W. Kc, N. M. Kretzer, C. G. Briseno, V. Durai, P. Bagadia, M. Haldar, J. Schonheit, F. Rosenbauer, T. L. Murphy, and K. M. Murphy. 2015. Batf3 maintains autoactivation of Irf8 for commitment of a CD8alpha(＋) conventional DC clonogenic progenitor. Nat. Immunol. 16: 708-717. https://doi.org/10.1038/ni.3197
  7. Schlitzer, A., V. Sivakamasundari, J. Chen, H. R. Sumatoh, J. Schreuder, J. Lum, B. Malleret, S. Zhang, A. Larbi, F. Zolezzi, L. Renia, M. Poidinger, S. Naik, E. W. Newell, P. Robson, and F. Ginhoux. 2015. Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow. Nat. Immunol. 16: 718-728. https://doi.org/10.1038/ni.3200
  8. Geissmann, F., M. G. Manz, S. Jung, M. H. Sieweke, M. Merad, and K. Ley. 2010. Development of monocytes, macrophages, and dendritic cells. Science 327: 656-661. https://doi.org/10.1126/science.1178331
  9. Satpathy, A. T., X. Wu, J. C. Albring, and K. M. Murphy. 2012. Re(de)fining the dendritic cell lineage. Nat. Immunol. 13: 1145-1154. https://doi.org/10.1038/ni.2467
  10. Murphy, K. M. 2013. Transcriptional control of dendritic cell development. Adv. Immunol. 120: 239-267. https://doi.org/10.1016/B978-0-12-417028-5.00009-0
  11. Esashi, E., Y. H. Wang, O. Perng, X. F. Qin, Y. J. Liu, and S. S. Watowich. 2008. The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8. Immunity 28: 509-520. https://doi.org/10.1016/j.immuni.2008.02.013
  12. Li, Z., and T. M. Rana. 2014. Therapeutic targeting of microRNAs: current status and future challenges. Nat. Rev. Drug Discov. 13: 622-638.
  13. Ha, M., and V. N. Kim. 2014. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 15: 509-524. https://doi.org/10.1038/nrm3838
  14. Johanson, T. M., J. P. Skinner, A. Kumar, Y. Zhan, A. M. Lew, and M. M. Chong. 2014. The role of microRNAs in lymphopoiesis. Int. J .Hematol. 100: 246-253. https://doi.org/10.1007/s12185-014-1606-y
  15. Smyth, L. A., D. A. Boardman, S. L. Tung, R. Lechler, and G. Lombardi. 2015. MicroRNAs affect dendritic cell function and phenotype. Immunology 144: 197-205. https://doi.org/10.1111/imm.12390
  16. Mildner, A., E. Chapnik, O. Manor, S. Yona, K. W. Kim, T. Aychek, D. Varol, G. Beck, Z. B. Itzhaki, E. Feldmesser, I. Amit, E. Hornstein, and S. Jung. 2013. Mononuclear phagocyte miRNome analysis identifies miR-142 as critical regulator of murine dendritic cell homeostasis. Blood 121: 1016-1027. https://doi.org/10.1182/blood-2012-07-445999
  17. Karrich, J. J., L. C. Jachimowski, M. Libouban, A. Iyer, K. Brandwijk, E. W. Taanman-Kueter, M. Nagasawa, E. C. de Jong, C. H. Uittenbogaart, and B. Blom. 2013. MicroRNA-146a regulates survival and maturation of human plasmacytoid dendritic cells. Blood 122: 3001-3009.
  18. Su, X., C. Qian, Q. Zhang, J. Hou, Y. Gu, Y. Han, Y. Chen, M. Jiang, and X. Cao. 2013. miRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a regulator of Notch1. Nat. Commun. 4: 2903.
  19. Agudo, J., A. Ruzo, N. Tung, H. Salmon, M. Leboeuf, D. Hashimoto, C. Becker, L. A. Garrett-Sinha, A. Baccarini, M. Merad, and B. D. Brown. 2014. The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids. Nat. Immunol. 15: 54-62. https://doi.org/10.1038/ni.2767
  20. Park, H., X. Huang, C. Lu, M. S. Cairo, and X. Zhou. 2015. MicroRNA-146a and microRNA-146b regulate human dendritic cell apoptosis and cytokine production by targeting TRAF6 and IRAK1 proteins. J. Biol. Chem. 290: 2831-2841. https://doi.org/10.1074/jbc.M114.591420
  21. Johanson, T. M., M. Cmero, J. Wettenhall, A. M. Lew, Y. Zhan, and M. M. Chong. 2015. A microRNA expression atlas of mouse dendritic cell development. Immunol. Cell Biol. 93: 480-485. https://doi.org/10.1038/icb.2014.109
  22. Park, S. H., C. Cheong, J. Idoyaga, J. Y. Kim, J. H. Choi, Y. Do, H. Lee, J. H. Jo, Y. S. Oh, W. Im, R. M. Steinman, and C. G. Park. 2008. Generation and application of new rat monoclonal antibodies against synthetic FLAG and OLLAS tags for improved immunodetection. J. Immunol. Methods 331: 27-38. https://doi.org/10.1016/j.jim.2007.10.012
  23. Inaba, K., W. J. Swiggard, R. M. Steinman, N. Romani, G. Schuler, and C. Brinster. 2009. Isolation of dendritic cells. Curr. Protoc. Immunol. Chapter 3: Unit 3.7
  24. Real, F. M., R. Sekido, D. G. Lupianez, R. Lovell-Badge, R. Jimenez, and M. Burgos. 2013. A microRNA (mmu-miR-124) prevents Sox9 expression in developing mouse ovarian cells. Biol. Reprod. 89: 78.
  25. Darrasse-Jeze, G., S. Deroubaix, H. Mouquet, G. D. Victora, T. Eisenreich, K. H. Yao, R. F. Masilamani, M. L. Dustin, A. Rudensky, K. Liu, and M. C. Nussenzweig. 2009. Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. J. Exp. Med. 206: 1853-1862. https://doi.org/10.1084/jem.20090746
  26. Choi, J. H., C. Cheong, D. B. Dandamudi, C. G. Park, A. Rodriguez, S. Mehandru, K. Velinzon, I. H. Jung, J. Y. Yoo, G. T. Oh, and R. M. Steinman. 2011. Flt3 signaling-dependent dendritic cells protect against atherosclerosis. Immunity 35: 819-831. https://doi.org/10.1016/j.immuni.2011.09.014
  27. Dweep, H., and N. Gretz. 2015. miRWalk2.0: a comprehensive atlas of microRNA-target interactions. Nat. Methods 12: 697.
  28. Cisse, B., M. L. Caton, M. Lehner, T. Maeda, S. Scheu, R. Locksley, D. Holmberg, C. Zweier, N. S. den Hollander, S. G. Kant, W. Holter, A. Rauch, Y. Zhuang, and B. Reizis. 2008. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135: 37-48. https://doi.org/10.1016/j.cell.2008.09.016
  29. Naik, S. H., A. I. Proietto, N. S. Wilson, A. Dakic, P. Schnorrer, M. Fuchsberger, M. H. Lahoud, M. O'Keeffe, Q. X. Shao, W. F. Chen, J. A. Villadangos, K. Shortman, and L. Wu. 2005. Cutting edge: generation of splenic CD8＋ and CD8- dendritic cell equivalents in Fms-like tyrosine kinase 3 ligand bone marrow cultures. J. Immunol. 174: 6592-6597. https://doi.org/10.4049/jimmunol.174.11.6592
  30. Naik, S. H., P. Sathe, H. Y. Park, D. Metcalf, A. I. Proietto, A. Dakic, S. Carotta, M. O'Keeffe, M. Bahlo, A. Papenfuss, J. Y. Kwak, L. Wu, and K. Shortman. 2007. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat. Immunol. 8: 1217-1226. https://doi.org/10.1038/ni1522
  31. Liu, K., G. D. Victora, T. A. Schwickert, P. Guermonprez, M. M. Meredith, K. Yao, F. F. Chu, G. J. Randolph, A. Y. Rudensky, and M. Nussenzweig. 2009. In vivo analysis of dendritic cell development and homeostasis. Science 324: 392-397.
  32. Kozomara, A., and S. Griffiths-Jones. 2014. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 42: D68-D73. https://doi.org/10.1093/nar/gkt1181
  33. Qiu, S., Y. Feng, G. LeSage, Y. Zhang, C. Stuart, L. He, Y. Li, Y. Caudle, Y. Peng, and D. Yin. 2015. Chronic morphine-induced microRNA-124 promotes microglial immunosuppression by modulating P65 and TRAF6. J. Immunol. 194: 1021-1030. https://doi.org/10.4049/jimmunol.1400106
  34. Baudet, M. L., K. H. Zivraj, C. breu-Goodger, A. Muldal, J. Armisen, C. Blenkiron, L. D. Goldstein, E. A. Miska, and C. E. Holt. 2012. miR-124 acts through CoREST to control onset of Sema3A sensitivity in navigating retinal growth cones. Nat. Neurosci. 15: 29-38. https://doi.org/10.1038/nn.2979
  35. Sonntag, K. C., T. U. Woo, and A. M. Krichevsky. 2012. Converging miRNA functions in diverse brain disorders: a case for miR-124 and miR-126. Exp. Neurol. 235: 427-435. https://doi.org/10.1016/j.expneurol.2011.11.035