Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice.

Pulendran, Bali; Lingappa, Jai; Kennedy, Mark; Smith, Jeffrey L.; Teepe, Mark; Rudensky, Alexander Y.; Maliszewski, Charles R.; Maraskovsky, Eugene

doi:10.4049/jimmunol.159.5.2222

Cited by 386 publications

(2 citation statements)

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“…Systemic application of Flt3L for several days promotes preDC proliferation in the BM. 23 Similarly, a general paucity of cDCs leads to elevated systemic Flt3L levels, which, in a progenitor-progeny feedback mechanism, increases the preDC output from the BM. 24 However, this feedback mechanism only adapts the quantity of cDCs and not the developmental stage of an individual cell in the tissue.…”

Section: Resultsmentioning

confidence: 99%

Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks

Ugur,

Labios,

Fenton

et al. 2023

Immunity

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Section: Resultsmentioning

confidence: 99%

Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks

Ugur,

Labios,

Fenton

et al. 2023

Immunity

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“…Among these findings is the key developmental signal for cDCs during hematopoiesis through the engagement of fms-like tyrosine kinase 3 (FLT3) by its ligand FLT3L and downstream activation of STAT3 [9]. Exogenous injection of FLT3L increases abundance of cDCs in vivo but there have not been reports of pathogenicity associated with high amounts of FLT3L [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Leukemic mutation FLT3-ITD is retained in dendritic cells and disrupts their homeostasis leading to expanded Th17 frequency

Flynn,

Long,

Kosaka

et al. 2023

Preprint

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Dendritic cells (DC) are mediators of adaptive immune responses to pathogens and tumors. DC development is determined by signaling through the receptor tyrosine kinase Fms-like tyrosine kinase 3 (FLT3) in bone marrow myeloid progenitors. Recently the naming conventions for DC phenotypes have been updated to distinguish between Conventional DCs (cDCs) and plasmacytoid DCs (pDCs). Activating mutations of FLT3, including Internal Tandem Duplication (FLT3-ITD), are associated with poor prognosis for leukemia patients. To date, there is little information on the effects of FLT3-ITD in DC biology. We examined the cDC phenotype and frequency in bone marrow aspirates from patients with acute myeloid leukemia (AML) to understand the changes to cDCs associated with FLT3-ITD. When compared to healthy donor (HD) we found that a subset of FLT3-ITD+ AML patient samples have overrepresented populations of cDCs and disrupted phenotypes. Using a mouse model of FLT3-ITD+ AML, we found that cDCs were increased in percentage and number compared to control wild-type (WT) mice. Single cell RNA-seq identified FLT3-ITD+ cDCs as skewed towards a cDC2 T-bet- phenotype, previously shown to promote Th17 T cells. We assessed the phenotypes of CD4+ T cells in the AML mice and found significant enrichment of both Treg and Th17 CD4+ T cells. Furthermore, co-culture of AML mouse-derived DCs and naiive OT-II cells preferentially skewed T cells into a Th17 phenotype. Together, our data suggests that FLT3-ITD+ leukemia-associated cDCs polarize CD4+ T cells into Th17 subsets, a population that has been shown to be negatively associated with survival in solid tumor contexts. This illustrates the complex tumor microenvironment of AML and highlights the need for further investigation into the effects of FLT3-ITD mutations on DC phenotypes.

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Alterations in Corneal Stromal Dendritic Cell Phenotype and Distribution in Inflammation

Hamrah¹

2003

Arch Ophthalmol

152

120

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Background: The normal corneal stroma is endowed with large numbers of resident dendritic cells (DCs). The purpose of this study was to examine the phenotype and distribution of these cells in inflammation. Methods: Normal and inflamed murine corneas were excised at different time points and immunofluorescence staining with multiple antibodies was performed by confocal microscopy on whole-mounted corneal stromas to characterize and evaluate the distribution of DCs in inflammation. Results: CD11c + CD11b + myeloid DCs were present throughout the anterior stroma. In the periphery of the normal cornea, nearly one half were major histocompatibility complex (MHC) class II + CD80 + CD86 + , while they were uniformly MHC class II − CD80 − CD86 − in the center. In inflammation, in addition to a significant increase in the number of DCs, a majority up-regulated their expression of MHC class II, CD80, and CD86, indicating their state of maturation. The up-regulation of MHC class II and costimulatory molecules on DCs was seen as early as 24 hours after induction of inflammation or transplantation. In addition to the CD11c + DCs in the anterior stroma, a CD11c − CD11b + population of monocytes/ macrophages was present almost exclusively in the posterior stroma of the cornea. These cells were found throughout all layers of the stroma, and in increased numbers, after induction of inflammation. Conclusion: The present study demonstrates, for the first time, the phenotypic changes and distribution of resident stromal DCs in corneal inflammation. Clinical Relevance: These novel data suggest that the cornea is capable of participating in immune and inflammatory responses by virtue of its own heterogeneous population of DCs.

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Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice.

Cited by 386 publications

References 0 publications

Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks

Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks

Leukemic mutation FLT3-ITD is retained in dendritic cells and disrupts their homeostasis leading to expanded Th17 frequency

Alterations in Corneal Stromal Dendritic Cell Phenotype and Distribution in Inflammation

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