Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo
Conventional dendritic cells (cDCs) are versatile activators of immune responses that develop as part of the myeloid lineage downstream of hematopoietic stem cells. We have recently shown that in mice precursors of cDCs, but not of other leukocytes, are marked by expression of DNGR-1/CLEC9A. To gene...
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doaj-794fcff4804748c4a970722eacc144e02020-11-24T22:24:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-04-01910.3389/fimmu.2018.00699361678Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In VivoJohanna Salvermoser0Johanna Salvermoser1Janneke van Blijswijk2Nikos E. Papaioannou3Stephan Rambichler4Stephan Rambichler5Maria Pasztoi6Dalia Pakalniškytė7Dalia Pakalniškytė8Neil C. Rogers9Selina J. Keppler10Tobias Straub11Tobias Straub12Caetano Reis e Sousa13Barbara U. Schraml14Barbara U. Schraml15Walter-Brendel-Centre for Experimental Medicine, University Hospital, LMU Munich, Planegg Martinsried, GermanyBiomedical Center, LMU Munich, Planegg Martinsried, GermanyImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomBiomedical Center, LMU Munich, Planegg Martinsried, GermanyWalter-Brendel-Centre for Experimental Medicine, University Hospital, LMU Munich, Planegg Martinsried, GermanyBiomedical Center, LMU Munich, Planegg Martinsried, GermanyBiomedical Center, LMU Munich, Planegg Martinsried, GermanyWalter-Brendel-Centre for Experimental Medicine, University Hospital, LMU Munich, Planegg Martinsried, GermanyBiomedical Center, LMU Munich, Planegg Martinsried, GermanyImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomTechnische Universität München, Klinikum Rechts der Isar, Institut für Klinische Chemie und Pathobiochemie, Munich, GermanyBiomedical Center, LMU Munich, Planegg Martinsried, GermanyCore Facility Bioinformatics, Biomedical Center (BMC), LMU Munich, Planegg Martinsried, GermanyImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomWalter-Brendel-Centre for Experimental Medicine, University Hospital, LMU Munich, Planegg Martinsried, GermanyBiomedical Center, LMU Munich, Planegg Martinsried, GermanyConventional dendritic cells (cDCs) are versatile activators of immune responses that develop as part of the myeloid lineage downstream of hematopoietic stem cells. We have recently shown that in mice precursors of cDCs, but not of other leukocytes, are marked by expression of DNGR-1/CLEC9A. To genetically deplete DNGR-1-expressing cDC precursors and their progeny, we crossed Clec9a-Cre mice to Rosa-lox-STOP-lox-diphtheria toxin (DTA) mice. These mice develop signs of age-dependent myeloproliferative disease, as has been observed in other DC-deficient mouse models. However, despite efficient depletion of cDC progenitors in these mice, cells with phenotypic characteristics of cDCs populate the spleen. These cells are functionally and transcriptionally similar to cDCs in wild type control mice but show somatic rearrangements of Ig-heavy chain genes, characteristic of lymphoid origin cells. Our studies reveal a previously unappreciated developmental heterogeneity of cDCs and suggest that the lymphoid lineage can generate cells with features of cDCs when myeloid cDC progenitors are impaired.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00699/fulldendritic celldevelopmentCLEC9A/DNGR-1DC depletionmyelopoiesislymphopoiesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Johanna Salvermoser Johanna Salvermoser Janneke van Blijswijk Nikos E. Papaioannou Stephan Rambichler Stephan Rambichler Maria Pasztoi Dalia Pakalniškytė Dalia Pakalniškytė Neil C. Rogers Selina J. Keppler Tobias Straub Tobias Straub Caetano Reis e Sousa Barbara U. Schraml Barbara U. Schraml |
spellingShingle |
Johanna Salvermoser Johanna Salvermoser Janneke van Blijswijk Nikos E. Papaioannou Stephan Rambichler Stephan Rambichler Maria Pasztoi Dalia Pakalniškytė Dalia Pakalniškytė Neil C. Rogers Selina J. Keppler Tobias Straub Tobias Straub Caetano Reis e Sousa Barbara U. Schraml Barbara U. Schraml Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo Frontiers in Immunology dendritic cell development CLEC9A/DNGR-1 DC depletion myelopoiesis lymphopoiesis |
author_facet |
Johanna Salvermoser Johanna Salvermoser Janneke van Blijswijk Nikos E. Papaioannou Stephan Rambichler Stephan Rambichler Maria Pasztoi Dalia Pakalniškytė Dalia Pakalniškytė Neil C. Rogers Selina J. Keppler Tobias Straub Tobias Straub Caetano Reis e Sousa Barbara U. Schraml Barbara U. Schraml |
author_sort |
Johanna Salvermoser |
title |
Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo |
title_short |
Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo |
title_full |
Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo |
title_fullStr |
Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo |
title_full_unstemmed |
Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo |
title_sort |
clec9a-mediated ablation of conventional dendritic cells suggests a lymphoid path to generating dendritic cells in vivo |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-04-01 |
description |
Conventional dendritic cells (cDCs) are versatile activators of immune responses that develop as part of the myeloid lineage downstream of hematopoietic stem cells. We have recently shown that in mice precursors of cDCs, but not of other leukocytes, are marked by expression of DNGR-1/CLEC9A. To genetically deplete DNGR-1-expressing cDC precursors and their progeny, we crossed Clec9a-Cre mice to Rosa-lox-STOP-lox-diphtheria toxin (DTA) mice. These mice develop signs of age-dependent myeloproliferative disease, as has been observed in other DC-deficient mouse models. However, despite efficient depletion of cDC progenitors in these mice, cells with phenotypic characteristics of cDCs populate the spleen. These cells are functionally and transcriptionally similar to cDCs in wild type control mice but show somatic rearrangements of Ig-heavy chain genes, characteristic of lymphoid origin cells. Our studies reveal a previously unappreciated developmental heterogeneity of cDCs and suggest that the lymphoid lineage can generate cells with features of cDCs when myeloid cDC progenitors are impaired. |
topic |
dendritic cell development CLEC9A/DNGR-1 DC depletion myelopoiesis lymphopoiesis |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2018.00699/full |
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