Analysis of transcription factors in thymic and CD34+ progenitor-derived plasmacytoid and myeloid dendritic cells: evidence for distinct expression profiles

Fohrer, Hélène; Audit, Isabelle; Sainz, Alexandre; Schmitt, C.; Dezutter‐Dambuyant, Colette; Dalloul, Ali

doi:10.1016/j.exphem.2003.10.007

Cited by 12 publications

(8 citation statements)

References 43 publications

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“…Such a model would be compatible with previously described inhibitory effects of ectopic Id2 on pDC development. 40 These cells show low endogenous PU.1 protein levels 41,42 and develop from progenitors via an M-CSF receptor-positive precursor pathway. 43 Several cell types might be capable of reconstituting LCs in vivo.…”

Section: Discussionmentioning

confidence: 99%

Differential involvement of PU.1 and Id2 downstream of TGF-β1 during Langerhans-cell commitment

Heinz

Platzer

Reisner

et al. 2006

Blood

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IntroductionCD1a ϩ human dendritic cells (DCs) comprise 2 functionally distinct subsets including Langerhans-type DCs (LCs) and dermal/ interstitial DCs (DDC-IDCs). [1][2][3][4] Both DC subsets arise from monopoietic intermediates in cultures of human CD34 ϩ hematopoietic progenitor cells. LCs develop from early monocytic cells identified as lysozyme ϩ , CD14 ϩ/Ϫ , CD11b Ϫ in serum-free cultures of CD34 ϩ cells in response to TGF-␤1. [5][6][7][8][9][10] Conversely, DDC-IDCs arise from more differentiated CD14 ϩ /CD11b ϩ monocytes in progenitor cultures. 8,9 In both instances, CD1a ϩ DC generation is associated with repression of monocyte features by cultured cells.In vivo, LC differentiation requires epithelial TGF-␤1. 11,12 TGF-␤1 addition to single-cell cultures of CD34 ϩ cells induces LC colony formation at the expense of monocyte/macrophagecontaining colonies. 7 In line with an early lineage instructive effect of TGF-␤1 on monocyte/LC (M/LC) progenitors, CD34 ϩ cells rapidly lose TGF-␤1-responsive LC differentiation potential upon in vitro expansion. 13 Transcriptional mechanisms underlying TGF-␤1-dependent LC commitment remain unknown. Recently, positive transcriptional regulators of LC induction have been identified. The ETS-domain transcription factor PU.1 is essential for myelopoiesis and myeloid DC development. [14][15][16][17][18][19] Recent studies demonstrated that ectopic PU.1 expression induces CD1a ϩ LC-like cells from CD34 ϩ progenitor cells 20 and induces DC fate in transformed chicken myeloid progenitors as well as in the absence of cytokines in human HL60 myeloblast/promyelocytic cells and monocyte clones. 21 Similarly the helix-loop-helix (HLH) regulatory protein inhibitor of DNA binding/differentiation 2 (Id2) is required for LC differentiation in vivo. 22 Id2 is induced in day-10-generated DC progenitors in response to TGF-␤1 stimulation, 22 suggesting that Id2 is functionally involved in TGF-␤1-dependent LC generation.Given previous observations that TGF-␤1 instructs progenitor cells to undergo LC differentiation, 6,7 together with recent reports that PU.1 and Id2 are candidates as positive regulators of LC commitment, 20,22 we considered the study of a possible functional interrelationship between TGF-␤1 and these factors to be of substantial importance. For our analysis, we used a model in which TGF-␤1 stimulation instructs freshly isolated or short-term expanded (Ͻ 96 hours) CD34 ϩ hematopoietic progenitor cells to undergo LC commitment. We demonstrate that TGF-␤1 induces PU.1 and Id2 in CD34 ϩ progenitor cells undergoing LC commitment. Since omission of TGF-␤1 abrogates LC differentiation and progenitors, in turn, developed into monocytes, we studied whether ectopic PU.1 or Id2 functionally replaces exogenous TGF-␤1 for these effects. Id2 repressed monocyte differentiation and PU.1 strongly promoted LC differentiation. However, PU.1 strictly required exogenous TGF-␤1. Our data support a model suggesting that PU.1 is generally increased by stimuli that induce CD1a ϩ myeloid DC generatio...

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Section: Discussionmentioning

confidence: 99%

Differential involvement of PU.1 and Id2 downstream of TGF-β1 during Langerhans-cell commitment

Heinz

Platzer

Reisner

et al. 2006

Blood

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“…6A) (36,37). To test for hemopoietic changes following LPS injection, we compared peripheral blood cell counts in TgR and FVB/N mice.…”

Section: Ache-r Excess Changes Hemopoietic Lps Responsesmentioning

confidence: 99%

Hydrolytic and Nonenzymatic Functions of Acetylcholinesterase Comodulate Hemopoietic Stress Responses

Grisaru¹,

Pick

Perry

et al. 2006

The Journal of Immunology

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Glucocorticoid-initiated granulocytosis, excessive proliferation of granulocytes, persists after cortisol levels are lowered, suggesting the involvement of additional stress mediator(s). In this study, we report that the stress-induced acetylcholinesterase variant, AChE-R, and its cleavable, cell-penetrating C-terminal peptide, ARP, facilitate granulocytosis. In postdelivery patients, AChE-R-expressing granulocyte counts increased concomitantly with serum cortisol and AChE activity levels, yet persisted after cortisol had declined. Ex vivo, mononuclear cells of adult peripheral blood responded to synthetic ARP26 by overproduction of hemopoietically active proinflammatory cytokines (e.g., IL-6, IL-10, and TNF-α). Physiologically relevant ARP26 levels promoted AChE gene expression and induced the expansion of cultured CD34+ progenitors and granulocyte maturation more effectively than cortisol, suggesting autoregulatory prolongation of ARP effects. In vivo, transgenic mice overexpressing human AChE-R, unlike matched controls, showed enhanced expression of the myelopoietic transcription factor PU.1 and maintained a stable granulocytic state following bacterial LPS exposure. AChE-R accumulation and the consequent inflammatory consequences can thus modulate immune responses to stress stimuli.

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“…Human ES cell lines H1 (NIH code WA01; passages [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] and H9 (NIH code WA09; passages 40 -44) were maintained in an undifferentiated state by weekly passages on mouse embryonic fibroblasts as previously described (25). A mouse bone marrow stromal cell line OP9 was obtained from Dr. T. Nakano (Research Institute for Microbial Diseases, Osaka University, Osaka, Japan).…”

Section: Cell Lines Cytokines and Mabsmentioning

confidence: 99%

Directed Differentiation of Human Embryonic Stem Cells into Functional Dendritic Cells through the Myeloid Pathway

Slukvin

Vodyanik

Thomson

et al. 2006

The Journal of Immunology

113

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We have established a system for directed differentiation of human embryonic stem (hES) cells into myeloid dendritic cells (DCs). As a first step, we induced hemopoietic differentiation by coculture of hES cells with OP9 stromal cells, and then, expanded myeloid cells with GM-CSF using a feeder-free culture system. Myeloid cells had a CD4+CD11b+CD11c+CD16+CD123lowHLA-DR− phenotype, expressed myeloperoxidase, and included a population of M-CSFR+ monocyte-lineage committed cells. Further culture of myeloid cells in serum-free medium with GM-CSF and IL-4 generated cells that had typical dendritic morphology; expressed high levels of MHC class I and II molecules, CD1a, CD11c, CD80, CD86, DC-SIGN, and CD40; and were capable of Ag processing, triggering naive T cells in MLR, and presenting Ags to specific T cell clones through the MHC class I pathway. Incubation of DCs with A23187 calcium ionophore for 48 h induced an expression of mature DC markers CD83 and fascin. The combination of GM-CSF with IL-4 provided the best conditions for DC differentiation. DCs obtained with GM-CSF and TNF-α coexpressed a high level of CD14, and had low stimulatory capacity in MLR. These data clearly demonstrate that hES cells can be used as a novel and unique source of hemopoietic and DC precursors as well as DCs at different stages of maturation to address essential questions of DC development and biology. In addition, because ES cells can be expanded without limit, they can be seen as a potential scalable source of cells for DC vaccines or DC-mediated induction of immune tolerance.

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Analysis of transcription factors in thymic and CD34+ progenitor-derived plasmacytoid and myeloid dendritic cells: evidence for distinct expression profiles

Cited by 12 publications

References 43 publications

Differential involvement of PU.1 and Id2 downstream of TGF-β1 during Langerhans-cell commitment

Differential involvement of PU.1 and Id2 downstream of TGF-β1 during Langerhans-cell commitment

Hydrolytic and Nonenzymatic Functions of Acetylcholinesterase Comodulate Hemopoietic Stress Responses

Directed Differentiation of Human Embryonic Stem Cells into Functional Dendritic Cells through the Myeloid Pathway

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