Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells
Open accessAbstract
Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical DCs (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. pDCs in Runx2-deficient mice developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes, including the chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the cell surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.
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DC cluster 2 may have contained plasmacytoid DCs.
“The plasmacytoid DC-specific TFs such as Tcf4 and Runx2 were more active in DC cluster 2 than other DC clusters 22-24 ; thus, DC cluster 2 may have contained plasmacytoid DCs.”
From Single-Cell RNA Sequencing to Dissect the Immunological Network of Autoimmune Myocarditis. (2020) · cites this paper as [24]
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Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245 · see citing works
Flagged first, then by citations
Research works printed but not linked: 32
- Asselin-Paturel C. Brizard G. Chemin K. Boonstra A. O’Garra A. Vicari A. Trinchieri G. 2005 Type I interferon dependence of plasmacytoid dendritic cell activation and migration. J. Exp. Med. 201: 1157– 1167 10.1084/jem.20041930 15795237 PMC2213121 · DOI
- Bao M. Liu Y.J. 2013 Regulation of TLR7/9 signaling in plasmacytoid dendritic cells. Protein Cell. 4: 40– 52 10.1007/s13238-012-2104-8 23132256 PMC3667388 · DOI
- Cervantes-Barragan L. Lewis K.L. Firner S. Thiel V. Hugues S. Reith W. Ludewig B. Reizis B. 2012 Plasmacytoid dendritic cells control T-cell response to chronic viral infection. Proc. Natl. Acad. Sci. USA. 109: 3012– 3017 10.1073/pnas.1117359109 22315415 PMC3286988 · DOI
- Chaperot L. Blum A. Manches O. Lui G. Angel J. Molens J.P. Plumas J. 2006 Virus or TLR agonists induce TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells. J. Immunol. 176: 248– 255 16365416
- Cisse B. Caton M.L. Lehner M. Maeda T. Scheu S. Locksley R. Holmberg D. Zweier C. den Hollander N.S. Kant S.G. 2008 Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell. 135: 37– 48 10.1016/j.cell.2008.09.016 18854153 PMC2631034 · DOI
- Collins A. Littman D.R. Taniuchi I. 2009 RUNX proteins in transcription factor networks that regulate T-cell lineage choice. Nat. Rev. Immunol. 9: 106– 115 10.1038/nri2489 19165227 PMC4231139 · DOI
- Colonna M. Trinchieri G. Liu Y.J. 2004 Plasmacytoid dendritic cells in immunity. Nat. Immunol. 5: 1219– 1226 10.1038/ni1141 15549123 · DOI
- Crozat K. Guiton R. Guilliams M. Henri S. Baranek T. Schwartz-Cornil I. Malissen B. Dalod M. 2010 Comparative genomics as a tool to reveal functional equivalences between human and mouse dendritic cell subsets. Immunol. Rev. 234: 177– 198 10.1111/j.0105-2896.2009.00868.x 20193019 · DOI
- Diacovo T.G. Blasius A.L. Mak T.W. Cella M. Colonna M. 2005 Adhesive mechanisms governing interferon-producing cell recruitment into lymph nodes. J. Exp. Med. 202: 687– 696 10.1084/jem.20051035 16147979 PMC2212867 · DOI
- Dijkman R. van Doorn R. Szuhai K. Willemze R. Vermeer M.H. Tensen C.P. 2007 Gene-expression profiling and array-based CGH classify CD4+CD56+ hematodermic neoplasm and cutaneous myelomonocytic leukemia as distinct disease entities. Blood. 109: 1720– 1727 10.1182/blood-2006-04-018143 17068154 · DOI
- Elpek K.G. Bellemare-Pelletier A. Malhotra D. Reynoso E.D. Lukacs-Kornek V. DeKruyff R.H. Turley S.J. 2011 Lymphoid organ-resident dendritic cells exhibit unique transcriptional fingerprints based on subset and site. PLoS ONE. 6: e23921 10.1371/journal.pone.0023921 21886840 PMC3158776 · DOI
- Ghosh H.S. Cisse B. Bunin A. Lewis K.L. Reizis B. 2010 Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity. 33: 905– 916 10.1016/j.immuni.2010.11.023 21145760 PMC3010277 · DOI
- Jia T. Serbina N.V. Brandl K. Zhong M.X. Leiner I.M. Charo I.F. Pamer E.G. 2008 Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection. J. Immunol. 180: 6846– 6853 18453605 PMC2386263
- Kamogawa-Schifter Y. Ohkawa J. Namiki S. Arai N. Arai K. Liu Y. 2005 Ly49Q defines 2 pDC subsets in mice. Blood. 105: 2787– 2792 10.1182/blood-2004-09-3388 15598811 · DOI
- Li H.S. Gelbard A. Martinez G.J. Esashi E. Zhang H. Nguyen-Jackson H. Liu Y.J. Overwijk W.W. Watowich S.S. 2011 Cell-intrinsic role for IFN-α-STAT1 signals in regulating murine Peyer patch plasmacytoid dendritic cells and conditioning an inflammatory response. Blood. 118: 3879– 3889 10.1182/blood-2011-04-349761 21828128 PMC3193265 · DOI
- Liu K. Nussenzweig M.C. 2010 Origin and development of dendritic cells. Immunol. Rev. 234: 45– 54 10.1111/j.0105-2896.2009.00879.x 20193011 · DOI
- Long F. 2012 Building strong bones: molecular regulation of the osteoblast lineage. Nat. Rev. Mol. Cell Biol. 13: 27– 38 10.1038/nrm3254 22189423 · DOI
- Mack M. Cihak J. Simonis C. Luckow B. Proudfoot A.E. Plachý J. Brühl H. Frink M. Anders H.J. Vielhauer V. 2001 Expression and characterization of the chemokine receptors CCR2 and CCR5 in mice. J. Immunol. 166: 4697– 4704 11254730
- Maeda T. Murata K. Fukushima T. Sugahara K. Tsuruda K. Anami M. Onimaru Y. Tsukasaki K. Tomonaga M. Moriuchi R. 2005 A novel plasmacytoid dendritic cell line, CAL-1, established from a patient with blastic natural killer cell lymphoma. Int. J. Hematol. 81: 148– 154 10.1532/IJH97.04116 15765784 · DOI
- Miller J.C. Brown B.D. Shay T. Gautier E.L. Jojic V. Cohain A. Pandey G. Leboeuf M. Elpek K.G. Helft J.; Immunological Genome Consortium 2012 Deciphering the transcriptional network of the dendritic cell lineage. Nat. Immunol. 13: 888– 899 10.1038/ni.2370 22797772 PMC3985403 · DOI
- Ngo V.N. Davis R.E. Lamy L. Yu X. Zhao H. Lenz G. Lam L.T. Dave S. Yang L. Powell J. Staudt L.M. 2006 A loss-of-function RNA interference screen for molecular targets in cancer. Nature. 441: 106– 110 10.1038/nature04687 16572121 · DOI
- Omatsu Y. Iyoda T. Kimura Y. Maki A. Ishimori M. Toyama-Sorimachi N. Inaba K. 2005 Development of murine plasmacytoid dendritic cells defined by increased expression of an inhibitory NK receptor, Ly49Q. J. Immunol. 174: 6657– 6662 15905504
- Otto F. Thornell A.P. Crompton T. Denzel A. Gilmour K.C. Rosewell I.R. Stamp G.W. Beddington R.S. Mundlos S. Olsen B.R. 1997 Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell. 89: 765– 771 10.1016/S0092-8674(00)80259-7 9182764 · DOI
- Reizis B. Bunin A. Ghosh H.S. Lewis K.L. Sisirak V. 2011 Plasmacytoid dendritic cells: recent progress and open questions. Annu. Rev. Immunol. 29: 163– 183 10.1146/annurev-immunol-031210-101345 21219184 PMC4160806 · DOI
- Sasaki I. Hoshino K. Sugiyama T. Yamazaki C. Yano T. Iizuka A. Hemmi H. Tanaka T. Saito M. Sugiyama M. 2012 Spi-B is critical for plasmacytoid dendritic cell function and development. Blood. 120: 4733– 4743 10.1182/blood-2012-06-436527 23065153 · DOI
- Satpathy A.T. Murphy K.M. Kc W. 2011 Transcription factor networks in dendritic cell development. Semin. Immunol. 23: 388– 397 10.1016/j.smim.2011.08.009 21924924 PMC4010935 · DOI
- Schlitzer A. Loschko J. Mair K. Vogelmann R. Henkel L. Einwächter H. Schiemann M. Niess J.H. Reindl W. Krug A. 2011 Identification of CCR9− murine plasmacytoid DC precursors with plasticity to differentiate into conventional DCs. Blood. 117: 6562– 6570 10.1182/blood-2010-12-326678 21508410 · DOI
- Seth S. Oberdörfer L. Hyde R. Hoff K. Thies V. Worbs T. Schmitz S. Förster R. 2011 CCR7 essentially contributes to the homing of plasmacytoid dendritic cells to lymph nodes under steady-state as well as inflammatory conditions. J. Immunol. 186: 3364– 3372 10.4049/jimmunol.1002598 21296980 · DOI
- Swiecki M. Gilfillan S. Vermi W. Wang Y. Colonna M. 2010 Plasmacytoid dendritic cell ablation impacts early interferon responses and antiviral NK and CD8(+) T cell accrual. Immunity. 33: 955– 966 10.1016/j.immuni.2010.11.020 21130004 PMC3588567 · DOI
- Tai L.H. Goulet M.L. Belanger S. Toyama-Sorimachi N. Fodil-Cornu N. Vidal S.M. Troke A.D. McVicar D.W. Makrigiannis A.P. 2008 Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC. J. Exp. Med. 205: 3187– 3199 10.1084/jem.20080718 19075287 PMC2605222 · DOI
- Tsou C.L. Peters W. Si Y. Slaymaker S. Aslanian A.M. Weisberg S.P. Mack M. Charo I.F. 2007 Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J. Clin. Invest. 117: 902– 909 10.1172/JCI29919 17364026 PMC1810572 · DOI · Paper page
- Wendland M. Czeloth N. Mach N. Malissen B. Kremmer E. Pabst O. Förster R. 2007 CCR9 is a homing receptor for plasmacytoid dendritic cells to the small intestine. Proc. Natl. Acad. Sci. USA. 104: 6347– 6352 10.1073/pnas.0609180104 17404233 PMC1851094 · DOI
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- Authors
- Sawai, C. M., Sisirak, V., Ghosh, H. S., Hou, E. Z., Ceribelli, M., Staudt, L. M., & Reizis, B.
- Affiliations
- Columbia University Irving Medical Center (US)
- National Institutes of Health (US)
- Corresponding author
- Reizis, Boris
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2013-10-07
- Volume
- 210
- Issue
- 11
- Pages
- 2151-2159
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC3804932
- OpenAlex
- W2161595265
- Cited by
- 133
- References
- 1
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 12 · 2023: 11 · 2022: 14 · 2021: 9 · 2020: 12 · 2019: 19 · 2018: 6 · 2017: 3 · 2016: 8 · 2015: 9 · 2014: 8
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Cancer Research Institute
- New York State Department of Health
- Leona M. and Harry B. Helmsley Charitable Trust
- National Institutes of Health (AI072571)
- National Institute of Allergy and Infectious Diseases (R01AI072571, AI072571)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- Runx2, plasmacytoid dendritic cells, dendritic cell development, dendritic cell migration, CCR5, CCR2, type I interferon, bone marrow, transcription factors
- MeSH terms
- Animals, Bone Marrow Cells, Cell Differentiation, Cell Movement, Dendritic Cells, Gene Expression Regulation, Humans, Mice, Inbred C57BL, Transcription Factors, Gene Deletion, Mice, Knockout, Receptors, CCR5, Core Binding Factor Alpha 1 Subunit, Mice, NK Cell Lectin-Like Receptor Subfamily A, Transcription Factor 7-Like 2 Protein
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