Transcription factor Etv6 regulates functional differentiation of cross-presenting classical dendritic cells

Lau, Colleen M.; Tiniakou, Ioanna; Perez, Oriana A.; Kirkling, Margaret E.; Yap, George; Hock, Hanno; Reizis, Boris

doi:10.1084/jem.20172323

Cited by 34 publications

(27 citation statements)

References 55 publications

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“…This, together with high transcription of TAP1 , points toward a prominent role of cDC1 in cross-presentation and CD8 T-cell activation, as has been shown for murine cDC1 ( 73 ). In support of this, bovine cDC1 transcribe ETV6 in the absence of ETS1 transcription, which was shown to be essential for optimal development of cross-priming function in murine cDC1 ( 74 ).…”

Section: Discussionmentioning

confidence: 85%

Precise Delineation and Transcriptional Characterization of Bovine Blood Dendritic-Cell and Monocyte Subsets

et al. 2018

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A clear-cut delineation of bovine bona fide dendritic cells (DC) from monocytes has proved challenging, given the high phenotypic and functional plasticity of these innate immune cells and the marked phenotypic differences between species. Here, we demonstrate that, based on expression of Flt3, CD172a, CD13, and CD4, a precise identification of bovine blood conventional DC type 1 and 2 (cDC1, cDC2), plasmacytoid DC (pDC), and monocytes is possible with cDC1 being Flt3+CD172adimCD13+CD4−, cDC2 being Flt3+CD172a+CD13−CD4−, pDC being Flt3+CD172adimCD13−CD4+, and monocytes being Flt3−CD172ahighCD13−CD4−. The phenotype of these subsets was characterized in further detail, and a subset-specific differential expression of CD2, CD5, CD11b, CD11c, CD14, CD16, CD26, CD62L, CD71, CD163, and CD205 was found. Subset identity was confirmed by transcriptomic analysis and subset-specific transcription of conserved key genes. We also sorted monocyte subsets based on their differential expression of CD14 and CD16. Classical monocytes (CD14+CD16−) clustered clearly apart from the two CD16+ monocyte subsets probably representing intermediate and non-classical monocytes described in human. The transcriptomic data also revealed differential gene transcription for molecules involved in antigen presentation, pathogen sensing, and migration, and therefore gives insights into functional differences between bovine DC and monocyte subsets. The identification of cell-type- and subset-specific gene transcription will assist in the quest for “marker molecules” that—when targeted by flow cytometry—will greatly facilitate research on bovine DC and monocytes. Overall, species comparisons will elucidate basic principles of DC and monocyte biology and will help to translate experimental findings from one species to another.

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Section: Discussionmentioning

confidence: 85%

Precise Delineation and Transcriptional Characterization of Bovine Blood Dendritic-Cell and Monocyte Subsets

et al. 2018

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“…Furthermore, deletion of TCF4 from mature pDCs induces the switch to dendritic morphology and expression of cDC gene signature ( Ceribelli et al., 2016 , Ghosh et al., 2010 ). Additional “resolution” between pDC and cDC expression programs is provided by transcription factor ETV6, which represses the cDC gene signature in pDCs and vice versa ( Lau et al., 2018 ). Altogether, these studies underscore a close relationship between pDC and the cDC lineages and reveal a unique transcriptional program that maintains pDCs in a “lymphoid-like” state and opposes alternative cDC fates.…”

Section: Main Textmentioning

confidence: 99%

Plasmacytoid Dendritic Cells: Development, Regulation, and Function

2019

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Plasmacytoid dendritic cells (pDCs) are a unique sentinel cell type that can detect pathogen-derived nucleic acids and respond with rapid and massive production of type I interferon. This review summarizes our current understanding of pDC biology, including transcriptional regulation, heterogeneity, role in antiviral immune responses, and involvement in immune pathology, particularly in autoimmune diseases, immunodeficiency, and cancer. We also highlight the remaining gaps in our knowledge and important questions for the field, such as the molecular basis of unique interferon-producing capacity of pDCs. A better understanding of cell type-specific positive and negative control of pDC function should pave the way for translational applications focused on this immune cell type.

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“…In addition, Zeb2 has been identified as an important regulator of Id2 expression, which allows pDC development from CDPs by suppressing the alternative cDC1 fate at a common precursor stage (22, 23). More recently Etv6 was shown to cooperate with IRF8 to refine cDC1-specific gene expression and repress the pDC gene expression signature indicating the close relationship between cDC1 and pDCs (61). Siglec-H, a canonical marker distinguishing mature pDCs from cDCs, is expressed at very early stages of differentiation, but does not denote a plasmacytoid commitment.…”

Section: Plasmacytoid Dendritic Cell Development From Myeloid and Lymmentioning

confidence: 99%

What Makes a pDC: Recent Advances in Understanding Plasmacytoid DC Development and Heterogeneity

Musumeci¹,

Lutz²,

Winheim³

et al. 2019

Front. Immunol.

105

100

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Dendritic cells (DCs) are professional antigen presenting cells (APCs) that originate in the bone marrow and are continuously replenished from hematopoietic progenitor cells. Conventional DCs (cDCs) and plasmacytoid DCs (pDCs) are distinguished by morphology and function, and can be easily discriminated by surface marker expression, both in mouse and man. Classification of DCs based on their ontology takes into account their origin as well as their requirements for transcription factor (TF) expression. cDCs and pDCs of myeloid origin differentiate from a common DC progenitor (CDP) through committed pre-DC stages. pDCs have also been shown to originate from a lymphoid progenitor derived IL-7R + FLT3 + precursor population containing cells with pDC or B cell potential. Technological advancements in recent years have allowed unprecedented resolution in the analysis of cell states, down to the single cell level, providing valuable information on the commitment, and dynamics of differentiation of all DC subsets. However, the heterogeneity and functional diversification of pDCs still raises the question whether different ontogenies generate restricted pDC subsets, or fully differentiated pDCs retain plasticity in response to challenges. The emergence of novel techniques for the integration of high-resolution data in individual cells promises interesting discoveries regarding DC development and plasticity in the near future.

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Transcription factor Etv6 regulates functional differentiation of cross-presenting classical dendritic cells

Cited by 34 publications

References 55 publications

Precise Delineation and Transcriptional Characterization of Bovine Blood Dendritic-Cell and Monocyte Subsets

Precise Delineation and Transcriptional Characterization of Bovine Blood Dendritic-Cell and Monocyte Subsets

Plasmacytoid Dendritic Cells: Development, Regulation, and Function

What Makes a pDC: Recent Advances in Understanding Plasmacytoid DC Development and Heterogeneity

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