<i>In vivo</i> conversion of BM plasmacytoid DC into CD11b<sup>+</sup> conventional DC during virus infection

Liou, Li Ying; Blasius, Amanda L.; Welch, Megan J.; Colonna, Marco; Oldstone, Michael B. A.; Zuniga, Elina J.

doi:10.1002/eji.200838282

Cited by 23 publications

(22 citation statements)

References 31 publications

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“…Type I IFN, which has been shown to drive the generation of BST2 ϩ Siglec H Ϫ PDC-like cells in the BM, which convert to CDCs during lymphocytic choriomeningitis virus infection, was not produced by IEC and could thus be excluded as a relevant factor. 7,8 GM-CSF is not detectable in the serum in the steady state but increases during inflammation. 20 It has been assumed that GM-CSF is dispensable for DC development in the steady state but influences DC differentiation during inflammation by inducing the generation of "inflammatory" DCs from precursors.…”

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

“…6 It has been reported that a population of Siglec-H-negative PDC-like cells in murine BM, which is only present in lymphocytic choriomeningitis virus-infected mice is capable of differentiating into CDCs during viral infection in a type I interferon (IFN)-dependent manner. 7,8 The potential of PDCs or committed PDC precursors to differentiate into other DC subpopulations in the absence of infection is unknown.It has been assumed from the available data that PDCs fully differentiate in the BM, circulate in the blood, and then enter lymphoid organs and peripheral tissues. CDCs, however, are generated from circulating committed precursors (pre-CDCs), which differentiate locally in lymphoid and peripheral tissues under the control of growth factors, such as Fms-like tyrosine kinase 3 ligand (Flt3L).…”

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confidence: 99%

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Identification of CCR9− murine plasmacytoid DC precursors with plasticity to differentiate into conventional DCs

Schlitzer

Loschko

Mair

et al. 2011

Blood

104

109

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Whereas the final differentiation of conventional dendritic cells (CDCs) from committed precursors occurs locally in secondary lymphoid or peripheral tissues, plasmacytoid dendritic cells (PDCs) are thought to fully develop in the bone marrow from common DC progenitors before migrating to the periphery. In our study, we define, for the first time, a subpopulation of CCR9 ؊ major histocompatibility complex class II low PDCs in murine bone marrow, which express E2-2 and are immediate precursors of CCR9 ؉ fully differentiated PDCs. However, CCR9 IntroductionAlthough plasmacytoid dendritic cells (PDCs) express markers of the "lymphoid" lineage, they can be derived from both common myeloid and common lymphoid progenitors. 1 Several elegant studies have convincingly shown that PDCs arise from common dendritic cell (DC) progenitors (or pro-DCs) in the bone marrow (BM), 2,3 which have the additional potential to generate precursor cells committed to conventional dendritic cell (CDC) development (pre-CDCs). 4,5 In contrast, common DC progenitors derived precursor cells committed exclusively to PDC development have not been described. Generation of PDCs is dependent on transcription factor E2-2, which drives the expression of other key transcription factors involved in PDC development and function (IRF8, Spi-B, IRF7) as well as PDC-specific markers (BST2 and Siglec H in murine PDCs, BDCA2 in human PDCs). 6 It has been reported that a population of Siglec-H-negative PDC-like cells in murine BM, which is only present in lymphocytic choriomeningitis virus-infected mice is capable of differentiating into CDCs during viral infection in a type I interferon (IFN)-dependent manner. 7,8 The potential of PDCs or committed PDC precursors to differentiate into other DC subpopulations in the absence of infection is unknown.It has been assumed from the available data that PDCs fully differentiate in the BM, circulate in the blood, and then enter lymphoid organs and peripheral tissues. CDCs, however, are generated from circulating committed precursors (pre-CDCs), which differentiate locally in lymphoid and peripheral tissues under the control of growth factors, such as Fms-like tyrosine kinase 3 ligand (Flt3L). 4,9 Thus, the development of CDC subpopulations is shaped by the local microenvironment allowing adaptation to tissue-specific functions. This has been shown recently for DCs in the intestinal lamina propria whose development from precursors is driven by local growth factors and the enteric microbial flora. [10][11][12] It is so far not clear whether PDCs in the intestine or in other peripheral tissues exclusively derive from fully differentiated circulating PDCs 13 or whether they can also differentiate locally from committed precursor cells under the influence of the specific tissue microenvironment.In this study, we identify an immediate PDC precursor in murine BM, which is characterized by expression of the transcription factor E2-2, PDC-specific markers (BST2, Siglec H), and production of type I IFN but lack of CCR9 and lo...

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Identification of CCR9− murine plasmacytoid DC precursors with plasticity to differentiate into conventional DCs

Schlitzer

Loschko

Mair

et al. 2011

Blood

104

109

View full text Add to dashboard Cite

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“…Furthermore, in addition to ChemR23, CXCR4 has been shown to direct the migration of pDCs (38). Alternatively, the decrease in pDCs may not represent altered recruitment, but could be the result of CS-induced maturation and differentiation of this immature DC subset into cDCs (39). Finally, the CS-induced reduction of pDCs could also result from a defect in available circulating pDCs or their precursors (40).…”

Section: Dcs In Chemr23mentioning

confidence: 99%

The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation

Demoor

Bracke

Dupont

et al. 2011

The Journal of Immunology

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Chronic obstructive pulmonary disease is mainly triggered by cigarette smoke (CS) and progresses even after smoking cessation. CS induces an exaggerated influx of inflammatory cells to the bronchoalveolar space and lung parenchyma, likely resulting from a complex interplay between chemoattractants and their respective receptors. In a murine CS model of chronic obstructive pulmonary disease, we studied the importance of chemokine-like receptor ChemR23 for the induction and resolution of inflammation in CS-exposed lungs. Subacute and chronic CS exposure increased protein levels of the ChemR23 ligand and chemoattractant, chemerin, in bronchoalveolar lavage (BAL) fluid of wild-type (WT) mice. Moreover, the proinflammatory chemokines CXCL1, CCL2, and CCL20 were increased in the airways of CS-exposed WT mice, accompanied by a massive accumulation of inflammatory neutrophils and monocytes, CD11bhiCD103− and CD11bloCD103+ dendritic cells (DCs), and CD4+ and CD8+ T cells. The lung parenchyma of WT mice was infiltrated with inflammatory neutrophils, CD11bhiCD103− DCs, and activated CD4+ T cells after CS exposure. CS-induced inflammation was severely attenuated in BAL fluid and lungs of ChemR23 knockout mice with regard to the induction of inflammatory chemokines and the recruitment of inflammatory cells. Neutrophils and CD8+ T cells persisted in the airways of WT mice, as did the airway-derived conventional DCs in the mediastinal lymph nodes, for at least 14 d after smoking cessation. In the BAL fluid of CS-exposed ChemR23 knockout mice, there was a remarkable delayed accumulation of T cells 14 d after the final exposure. Our data support a role for ChemR23 in directing innate and adaptive immune cells to CS-exposed lungs.

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“…Do low pDC numbers arise from a maturation defect? Alternatively, perhaps there is greater differentiation of pDCs to conventional DCs [65,66]? It will also be important to determine the influence of environmental factors, such as maternal smoking, gut bacterial colonisation and diet, on the ontogeny of pDCs in early life.…”

Section: Introductionmentioning

confidence: 99%

The plasmacytoid dendritic cell: at the cross-roads in asthma

et al. 2013

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The onset, progression and exacerbations of asthma are frequently associated with viral infections of the lower respiratory tract. An emerging paradigm suggests that this relationship may be underpinned by a defect in the host's antiviral response, typified by the impaired production of type I and type III interferons (IFNs). The failure to control viral burden probably causes damage to the lung architecture and contributes to an aberrant immune response, which together compromise lung function.Although a relatively rare cell type, the plasmacytoid dendritic cell dedicates much of its transcriptome to the synthesis of IFNs and is pre-armed with virus-sensing pattern recognition receptors. Thus, plasmacytoid dendritic cells are specialised to ensure early viral detection and the rapid induction of the antiviral state to block viral replication and spread. In addition, plasmacytoid dendritic cells can limit immunopathology, and promote peripheral tolerance to prevent allergic sensitisation to harmless antigens, possibly through the induction of regulatory T-cells. Thus, this enigmatic cell may lie at an important intersection, orchestrating the immediate phase of antiviral immunity to effect viral clearance while regulating tolerance.Here, we review the evidence to support the hypothesis that a primary defect in plasmacytoid dendritic function may underlie the development of asthma. @ERSpublications A review of the evidence on the role of plasmacytoid dendritic function in the development of asthma

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In vivo conversion of BM plasmacytoid DC into CD11b⁺ conventional DC during virus infection

Cited by 23 publications

References 31 publications

Identification of CCR9− murine plasmacytoid DC precursors with plasticity to differentiate into conventional DCs

Identification of CCR9− murine plasmacytoid DC precursors with plasticity to differentiate into conventional DCs

The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation

The plasmacytoid dendritic cell: at the cross-roads in asthma

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In vivo conversion of BM plasmacytoid DC into CD11b+ conventional DC during virus infection

Cited by 23 publications

References 31 publications

Identification of CCR9− murine plasmacytoid DC precursors with plasticity to differentiate into conventional DCs

Identification of CCR9− murine plasmacytoid DC precursors with plasticity to differentiate into conventional DCs

The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation

The plasmacytoid dendritic cell: at the cross-roads in asthma

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In vivo conversion of BM plasmacytoid DC into CD11b⁺ conventional DC during virus infection