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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Published in:Frontiers in immunology 2018-04, Vol.9, p.699
Main Authors: Salvermoser, Johanna, van Blijswijk, Janneke, Papaioannou, Nikos E, Rambichler, Stephan, Pasztoi, Maria, Pakalniškytė, Dalia, Rogers, Neil C, Keppler, Selina J, Straub, Tobias, Reis e Sousa, Caetano, Schraml, Barbara U
Format: Article
Language:English
Subjects:
Animals
CLEC9A/DNGR-1
DC depletion
dendritic cell
Dendritic Cells - drug effects
Dendritic Cells - immunology
development
Diphtheria Toxin - pharmacology
Immunology
Lectins, C-Type - genetics
Lectins, C-Type - immunology
lymphopoiesis
Mice
myelopoiesis
Receptors, Immunologic - genetics
Receptors, Immunologic - immunology
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Summary: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 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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2018.00699