TCF4-Targeting miR-124 is Differentially Expressed amongst Dendritic Cell Subsets
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
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).
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).
참고문헌 (35)
- Steinman, R. M., "Decisions about dendritic cells: past, present, and future", Annu. Rev. Immunol, 30, pp.1~22 (2012)
- Park, C. G., "Vaccine strategies utilizing C-type lectin receptors on dendritic cells in vivo", Clin. Exp. Vaccine Res, 3, pp.149~154 (2014)
- Steinman, R. M., "Features of the dendritic cell lineage", Immunol. Rev, 234, pp.5~17 (2010)
- Kingston, D., "The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis", Blood, 114, pp.835~843 (2009)
- Onai, N., "A clonogenic progenitor with prominent plasmacytoid dendritic cell developmental potential", Immunity, 38, pp.943~957 (2013)
- Grajales-Reyes, G. E., "Batf3 maintains autoactivation of Irf8 for commitment of a CD8alpha(＋) conventional DC clonogenic progenitor", Nat. Immunol, 16, pp.708~717 (2015)
- Schlitzer, A., "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, pp.718~728 (2015)
- Geissmann, F., "Development of monocytes, macrophages, and dendritic cells", Science, 327, pp.656~661 (2010)
- Satpathy, A. T., "Re(de)fining the dendritic cell lineage", Nat. Immunol, 13, pp.1145~1154 (2012)
- Murphy, K. M., "Transcriptional control of dendritic cell development", Adv. Immunol, 120, pp.239~267 (2013)
- Esashi, E., "The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8", Immunity, 28, pp.509~520 (2008)
- Li, Z., "Therapeutic targeting of micro-RNAs: current status and future challenges", Nat. Rev. Drug Discov, 13, pp.622~638 (2014)
- Ha, M., "Regulation of microRNA biogenesis", Nat. Rev. Mol. Cell Biol, 15, pp.509~524 (2014)
- Johanson, T. M., "The role of microRNAs in lymphopoiesis", Int. J .Hematol, 100, pp.246~253 (2014)
- Smyth, L. A., "MicroRNAs affect dendritic cell function and phenotype", Immunology, 144, pp.197~205 (2015)
- Mildner, A., "Mononuclear phagocyte miRNome analysis identifies miR-142 as critical regulator of murine dendritic cell homeostasis", Blood, 121, pp.1016~1027 (2013)
- Karrich, J. J., "MicroRNA-146a regulates survival and maturation of human plasmacytoid dendritic cells", Blood, 122, pp.3001~3009 (2013)
- Su, X., "miRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a regulator of Notch1", Nat. Commun, 4, pp.2903~ (2013)
- Agudo, J., "The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids", Nat. Immunol, 15, pp.54~62 (2014)
- Park, H., "MicroRNA-146a and microRNA-146b regulate human dendritic cell apoptosis and cytokine production by targeting TRAF6 and IRAK1 proteins", J. Biol. Chem, 290, pp.2831~2841 (2015)
- Johanson, T. M., "A microRNA expression atlas of mouse dendritic cell development", Immunol. Cell Biol, 93, pp.480~485 (2015)
- Park, S. H., "Generation and application of new rat monoclonal antibodies against synthetic FLAG and OLLAS tags for improved immunodetection", J. Immunol. Methods, 331, pp.27~38 (2008)
- Inaba, K., "Isolation of dendritic cells", Curr. Protoc. Immunol (2009)
- Real, F. M., "A microRNA (mmu-miR-124) prevents Sox9 expression in developing mouse ovarian cells", Biol. Reprod, 89, pp.78~ (2013)
- Darrasse-Jeze, G., "Feedback control of regulatory T cell homeostasis by dendritic cells in vivo", J. Exp. Med, 206, pp.1853~1862 (2009)
- Choi, J. H., "Flt3 signaling-dependent dendritic cells protect against atherosclerosis", Immunity, 35, pp.819~831 (2011)
- Dweep, H., "miRWalk2.0: a comprehensive atlas of microRNA-target interactions", Nat. Methods, 12, pp.697~ (2015)
- Cisse, B., "Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development", Cell, 135, pp.37~48 (2008)
- Naik, S. H., "Cutting edge: generation of splenic CD8＋and CD8−dendritic cell equivalents in Fms-like tyrosine kinase 3 ligand bone marrow cultures", J. Immunol, 174, pp.6592~6597 (2005)
- Naik, S. H., "Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo", Nat. Immunol, 8, pp.1217~1226 (2007)
- Liu, K., "In vivo analysis of dendritic cell development and homeostasis", Science, 324, pp.392~397 (2009)
- Kozomara, A., "miRBase: annotating high confidence microRNAs using deep sequencing data", Nucleic Acids Res, 42, pp.D68~D73 (2014)
- Qiu, S., "Chronic morphine-induced microRNA-124 promotes microglial immunosuppression by modulating P65 and TRAF6", J. Immunol, 194, pp.1021~1030 (2015)
- Baudet, M. L., "miR-124 acts through CoREST to control onset of Sema3A sensitivity in navigating retinal growth cones", Nat. Neurosci, 15, pp.29~38 (2012)
- Sonntag, K. C., "Converging miRNA functions in diverse brain disorders: a case for miR-124 and miR-126", Exp. Neurol, 235, pp.427~435 (2012)