Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling

Robbins, Scott H.; Walzer, Thierry; Dembélé, Doulaye; Thibault, Christelle; Defays, Axel; Bessou, Gilles; Xu, Huichun; Vivier, Éric; Sellars, MacLean; Pierre, Philippe; Sharp, Franck R; Chan, Susan; Kastner, Philippe; Dalod, Marc

doi:10.1186/gb-2008-9-1-r17

Cited by 459 publications

(605 citation statements)

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“…Here we not only confirmed prominent mRNA and protein expression of E2-2 in pDC, but, in addition, provide evidence to suggest that Id factors when overexpressed most likely antagonize E2-2 activity in progenitor cells, thereby blocking development into the pDC lineage. Of notice, we and others [42] did not detect high expression of the other Eproteins HEB, E12, or E47 in pDC. To our surprise we observed, however, that overexpression of the other E-proteins in human progenitor cells promoted in vitro pDC development to some extent (data not shown).…”

Section: Discussioncontrasting

confidence: 51%

“…In line with this, pDC development is enhanced in Id2 deficient mice [25]. Recently, a GeneChip analysis on mouse and human leukocytes showed that E2-2 is expressed at high levels in pDC, while Id2 was high in cDC [42]. Here we not only confirmed prominent mRNA and protein expression of E2-2 in pDC, but, in addition, provide evidence to suggest that Id factors when overexpressed most likely antagonize E2-2 activity in progenitor cells, thereby blocking development into the pDC lineage.…”

Section: Discussionmentioning

confidence: 64%

“…Here we describe that E2-2 and Spi-B cooperate in pDC development. Of notice, both IRF-4 and IRF-8 are highly expressed in human pDC ( [42,51,52], and H. Schmidlin and B. Blom, unpublished results) and crucially involved in murine pDC development [14,16]. It is therefore tempting to speculate that Spi-B, in addition to contributing to the downregulation of Id2 expression, may in complex with E2-2 and IRF-4 and/or IRF-8 bind to a juxtaposed E-box and EICE to promote pDC development.…”

Section: Discussionmentioning

confidence: 99%

“…This, however, does not exclude the role of IRF-8 in human pDC development as the protein may already be present at high level, whereas Spi-B and E2-2 may be the limiting factors in commitment to the pDC lineage. Alternatively, IRF-4, which is highly expressed in pDC [42], may exhibit a redundant role. This notion is supported by the fact that IRF4/IRF8 double deficient mice have even less pDCa compared with the single knockout mice [53].…”

Section: Discussionmentioning

confidence: 99%

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Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix‐loop‐helix factor E2‐2 and the Ets factor Spi‐B

et al. 2008

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Plasmacytoid dendritic cells (pDC) are central players in the innate and adaptive immune response against viral infections. The molecular mechanism that underlies pDC development from progenitor cells is only beginning to be elucidated. Previously, we reported that the Ets factor Spi-B and the inhibitors of DNA binding protein 2 (Id2) or Id3, which antagonize E-protein activity, are crucially involved in promoting or impairing pDC development, respectively. Here we show that the basic helix-loop-helix protein E2-2 is predominantly expressed in pDC, but not in their progenitor cells or conventional DC. Forced expression of E2-2 in progenitor cells stimulated pDC development. Conversely, inhibition of E2-2 expression by RNA interference impaired the generation of pDC suggesting a key role of E2-2 in development of these cells. Notably, Spi-B was unable to overcome the Id2 enforced block in pDC development and moreover Spi-B transduced pDC expressed reduced Id2 levels. This might indicate that Spi-B contributes to pDC development by promoting E2-2 activity. Consistent with notion, simultaneous overexpression of E2-2 and Spi-B in progenitor cells further stimulated pDC development. Together our results provide additional insight into the transcriptional network controlling pDC development as evidenced by the joint venture of E2-2 and Spi-B.Key words: E2-2/TCF4 Á E-proteins Á Human development Á Plasmacytoid dendritic cell Á Spi-B Supporting Information available online See accompanying commentary by Esashi and Liu IntroductionThe ability of dendritic cells (DC) to capture and present antigenic peptides has established a function in both the adaptive and innate branches of the immune system. Extensive characterization of DC has revealed the existence of many different DC subsets with distinct cell surface phenotype, cytokine expression profile, and anatomical localization [1]. One member of the DC family is the plasmacytoid DC (pDC), which is hallmarked by their capacity to produce high levels of type I interferons and hence are also known as natural type I interferons producing cells [2]. Eur. J. Immunol. 2008. 38: 2389-2400 DOI 10.1002 HIGHLIGHTS 2389Frontline pDC are detected in blood and most tissues, including spleen, lymph nodes, and thymus [2,3]. Previously, we described that at least two developmental pathways exist for pDC, an extrathymic and an intrathymic pathway [4]. The requirements for the development of DC subsets are not fully understood. In mice it has been shown that conventional DC (cDC) and pDC can develop from minor Flt3 1 subpopulations within the common myeloid and the common lymphoid progenitor pools [5][6][7]. Recently, this pool was narrowed down to a DC committed precursor (pro-DC) that can only develop into cells of the DC lineages [8,9]. It is not clear yet at what point in DC development the commitment to a subpopulation is accomplished. Also, human pDC can be derived from both myeloid and lymphoid progenitor cells [10,11]. A better understanding of the molecular mechanisms that control...

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Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix‐loop‐helix factor E2‐2 and the Ets factor Spi‐B

et al. 2008

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“…Human PDC are usually identified as CD4 + , CD303 + (previously known as BDCA-2), and CD123 high , whereas mouse PDC are CD11c int , B220 + , SIGLEC-H + , and CD317 + 7 . Despite the difference in phenotypes of human and mouse PDC, PDC from both species exhibit a conserved genetic signature with some common genes (e.g., tlr7 ) 20 . Moreover, PDC exhibit specific transcription factors, such as the transcription factor E2-2 (also known as TCF4) or SPIB 7 .…”

Section: The Innate Immune Functions Of Plasmacytoid Dendritic Cellsmentioning

confidence: 99%

Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

Saas¹,

Varin²,

Perruche³

et al. 2017

F1000Res

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There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β). Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases. Recent data support the idea that the glycolytic pathway (or glycolysis), as well as lipid metabolism (including both cholesterol and fatty acid metabolism) may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR) 7/9 triggering. Some differences may be related to the origin of PDC (human versus mouse PDC or blood-sorted versus FLT3 ligand stimulated-bone marrow-sorted PDC). The kinetics of glycolysis may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR, explaining a delayed glycolysis. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR]) in PDC or through limiting intracellular cholesterol pool size (by statins or LXR agonists) in these cells. Finally, lipid-activated nuclear receptors ( i.e., LXR or peroxisome proliferator activated receptor) may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations where PDC play a detrimental role.

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Dendritic Cells in Hematopoietic Cell Transplantation

Mérad

Engleman

2015

Thomas’ Hematopoietic Cell Transplantation

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Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling

Cited by 459 publications

References 96 publications

Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix‐loop‐helix factor E2‐2 and the Ets factor Spi‐B

Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix‐loop‐helix factor E2‐2 and the Ets factor Spi‐B

Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

Dendritic Cells in Hematopoietic Cell Transplantation

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