Continuous Expression of the Transcription Factor E2-2 Maintains the Cell Fate of Mature Plasmacytoid Dendritic Cells

Ghosh, Hiyaa S.; Cisse, Babacar; Bunin, Anna; Lewis, Kanako L.; Reizis, Boris

doi:10.1016/j.immuni.2010.11.023

Cited by 242 publications

(268 citation statements)

References 51 publications

(79 reference statements)

Supporting

Mentioning

246

Contrasting

Order By: Relevance

“…Mechanistically, E2-2 regulates a large pDC gene program including the direct regulation of other key transcription factors associated with pDC development, including IRF8, Bcl11a, and Spi-B. Interestingly, E2-2 also appears to repress genes associated with cDC subsets [110]. This was shown using an inducible Credeletion system whereby E2-2 was deleted in mature pDCs.…”

Section: The Balance Between E2-2 and Id2 Determines The Choice Betwementioning

confidence: 97%

Transcription factor networks in dendritic cell development

Satpathy

Murphy

2011

Seminars in Immunology

View full text Add to dashboard Cite

Dendritic cells (DCs) are a heterogeneous population within the mononuclear phagocyte system (MPS) that derive from bone marrow precursors. Commitment and specification of hematopoietic progenitors to the DC lineage is critical for the proper induction of both immunity and tolerance. This review summarizes the important cytokines and transcription factors required for differentiation of the DC lineage as well as further diversification into specific DC subsets. We highlight recent advances in the characterization of immediate DC precursors arising from the common myeloid progenitor (CMP). Particular emphasis is placed on the corresponding temporal expression of relevant factors involved in regulating developmental options.

show abstract

Section: The Balance Between E2-2 and Id2 Determines The Choice Betwementioning

confidence: 97%

Transcription factor networks in dendritic cell development

Satpathy

Murphy

2011

Seminars in Immunology

View full text Add to dashboard Cite

show abstract

“…Rather, these data suggest that the underlying cellular process defining the size of the pDC compartment may either result from more subtle variations in pDC proliferation or apoptosis not detectable in the context of the assays performed in this study or from more complex hematopoieticdependent factors, including but not limited to the presence of a key cytokine, cell-cell interaction with other hematopoietic cells, and/or the rate of hematopoietic differentiation of pDC. To that effect, a number of genes (Spib, Tcf4, Irf4, Irf8, and Flt3) have been shown to contribute to the hematopoietic differentiation of pDC (7,11,12,14,15). Of these genes, Spib and Flt3l (Flt3 ligand) are encoded on chromosome 7 between 51 and 53 Mb, comprised within the NOD.NZW-Chr7 congenic interval contributing to the size of the pDC compartment.…”

Section: Discussionmentioning

confidence: 99%

“…IFN regulatory factor (IRF)-8 also proved to be a key transcription factor in pDC differentiation and function, as Irf8-deficient mice presented with a much reduced proportion of pDC along with a deficiency in type I IFN production upon viral infection (13). More recent studies have proposed that the E2-2 transcription factor serves as a specific regulator of the pDC transcription profile, acting upstream of both Spi-B and IRF-8, and revealed its importance in the maintenance of the pDC fate (14,15). Therefore, the differentiation of pDC is dependent on the timely expression of specific transcription factors.…”

mentioning

confidence: 99%

The Size of the Plasmacytoid Dendritic Cell Compartment Is a Multigenic Trait Dominated by a Locus on Mouse Chromosome 7

Pelletier

Guimont-Desrochers

Ashton

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

Plasmacytoid dendritic cells (pDC) compose one of the many distinct dendritic cell subsets. The primary function of pDC is to potently produce type 1 IFNs upon stimulation, which is highly relevant in antiviral responses. Consequently, the ability to manipulate the size of the pDC compartment in vivo may increase the capacity to clear viral infections. In an attempt to identify genetic loci affecting the size of the pDC compartment, defined by both the proportion and absolute number of pDC, we undertook an unbiased genetic approach. Linkage analysis using inbred mouse strains identified a locus on chromosome 7 (Pdcc1) significantly linked to both the proportion and the absolute number of pDC in the spleen. Moreover, loci on either chromosome 11 (Pdcc2) or 9 (Pdcc3) modified the effect of Pdcc1 on chromosome 7 for the proportion and absolute number of pDC, respectively. Further analysis using mice congenic for chromosome 7 confirmed Pdcc1, demonstrating that variation within this genetic interval can regulate the size of the pDC compartment. Finally, mixed bone marrow chimera experiments showed that both the proportion and the absolute number of pDC are regulated by cell-intrinsic hematopoietic factors. Our findings highlight the multigenic regulation of the size of the pDC compartment and will facilitate the identification of genes linked to this trait.

show abstract

“…Similarly to cDCs, pDCs are also derived from bone marrow progenitors in an Flt3L-dependent manner. 20,21 The development of pDCs is promoted by the transcription factor basic helix-loop-helix transcription factor (E protein) 22,23 with the contribution of Spi-B transcription factor (Spi-1/PU.1 related). 24 …”

Section: Classes Of Dcsmentioning

confidence: 99%

Role and therapeutic value of dendritic cells in central nervous system autoimmunity

2014

View full text Add to dashboard Cite

Dendritic cells (DCs) are professional antigen-presenting cells that control the generation of adaptive immunity. Consequently, DCs have a central role in the induction of protective immunity to pathogens and also in the pathogenic immune response responsible for the development and progression of autoimmune disorders. Thus the study of the molecular pathways that control DC development and function is likely to result in new strategies for the therapeutic manipulation of the immune response. In this review, we discuss the role and therapeutic value of DCs in autoimmune diseases, with a special focus on multiple sclerosis. Cell Death and Differentiation (2015) 22, 215-224; doi:10.1038/cdd.2014; published online 29 August 2014 FactsDendritic cells (DCs) control central and peripheral tolerance through their effects on effector and regulatory T cells. Specific signaling pathways regulate the ability of different DC populations to promote effector and regulatory T-cell responses. Abnormalities in DC numbers, recruitment and function contribute to the pathology of multiple sclerosis (MS) and can be partially overcome by the use of disease-modifying therapies and the targeting of specific molecular pathways. Nanotechnology provides new tools for the modulation of DC activity in vivo and the therapeutic induction of antigenspecific tolerance in immune-mediated disorders. Open QuestionsAlthough DC populations that promote the development of forkhead box P3-positive (FoxP3 þ ) regulatory T cells (Tregs) have been identified, it is not yet clear whether these populations constitute separate tolerogenic DC lineages or represent alternative activation or maturation states of other DC populations. What are the different molecular pathways that control the DC's ability to prime effector or tolerogenic T-cell responses?There is an unmet clinical need for the development of methods for the efficient and consistent generation of tolerogenic DCs in vitro and in vivo that can be implemented in large-scale clinical setups.Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that control the activation and polarization of T cells into specific lineages and, consequently, the generation of antigen-specific antibody and T-cell responses. 1 In the context of an infectious challenge, the induction of pathogenspecific immune responses provides protective immunity to fight the infection. However, in the context of autoimmune diseases DCs regulate the balance between pathogenic and regulatory immune mechanisms, controlling disease onset and progression. Thus, DCs have a central role in the control of the adaptive immune response to pathogens and selftissues and therefore constitute potential targets for the therapeutic modulation of the immune response. In this review, we discus the role of DCs in autoimmune diseases, with a special emphasis on their role in the modulation of central nervous system (CNS) inflammation in MS. Received 12.6.14; accepted 23.6.14; Edited by H-U Simon; published online 29.8.14 Abbreviations: A...

show abstract

Continuous Expression of the Transcription Factor E2-2 Maintains the Cell Fate of Mature Plasmacytoid Dendritic Cells

Cited by 242 publications

References 51 publications

Transcription factor networks in dendritic cell development

Transcription factor networks in dendritic cell development

The Size of the Plasmacytoid Dendritic Cell Compartment Is a Multigenic Trait Dominated by a Locus on Mouse Chromosome 7

Role and therapeutic value of dendritic cells in central nervous system autoimmunity

Contact Info

Product

Resources

About