Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo

Salvermoser, Johanna; Blijswijk, Janneke van; Papaioannou, Nikos E.; Rambichler, Stephan; Pásztói, Mária; Pakalniškytė, Dalia; Rogers, Neil C.; Keppler, Selina J.; Straub, Tobias; Sousa, Caetano Reis e; Schraml, Barbara U.

doi:10.3389/fimmu.2018.00699

Cited by 18 publications

(23 citation statements)

References 89 publications

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“…Notably, YFP labeling also suggests an age-dependent heterogeneity of CD11b hi cells. Because monocytes and lymphoid progenitors can contribute to macrophage and DC-like cells, 1,11,17,[69][70][71] these cells could also be putative progenitors of CD11b hi and F4/80 hi cells in early life, which needs to be investigated.…”

Section: Discussionmentioning

confidence: 99%

The Kidney Contains Ontogenetically Distinct Dendritic Cell and Macrophage Subtypes throughout Development That Differ in Their Inflammatory Properties

Salei

Rambichler

Salvermoser

et al. 2020

JASN

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BackgroundMononuclear phagocytes (MPs), including macrophages, monocytes, and dendritic cells (DCs), are phagocytic cells with important roles in immunity. The developmental origin of kidney DCs has been highly debated because of the large phenotypic overlap between macrophages and DCs in this tissue.MethodsWe used fate mapping, RNA sequencing, flow cytometry, confocal microscopy, and histo-cytometry to assess the origin and phenotypic and functional properties of renal DCs in healthy kidney and of DCs after cisplatin and ischemia reperfusion–induced kidney injury.ResultsAdult kidney contains at least four subsets of MPs with prominent Clec9a-expression history indicating a DC origin. We demonstrate that these populations are phenotypically, functionally, and transcriptionally distinct from each other. We also show these kidney MPs exhibit unique age-dependent developmental heterogeneity. Kidneys from newborn mice contain a prominent population of embryonic-derived MHCIInegF4/80hiCD11blow macrophages that express T cell Ig and mucin domain containing 4 (TIM-4) and MER receptor tyrosine kinase (MERTK). These macrophages are replaced within a few weeks after birth by phenotypically similar cells that express MHCII but lack TIM-4 and MERTK. MHCII+F4/80hi cells exhibit prominent Clec9a-expression history in adulthood but not early life, indicating additional age-dependent developmental heterogeneity. In AKI, MHCIInegF4/80hi cells reappear in adult kidneys as a result of MHCII downregulation by resident MHCII+F4/80hi cells, possibly in response to prostaglandin E2 (PGE2). RNA sequencing further suggests MHCII+F4/80hi cells help coordinate the recruitment of inflammatory cells during renal injury.ConclusionsDistinct developmental programs contribute to renal DC and macrophage populations throughout life, which could have important implications for therapies targeting these cells.

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Section: Discussionmentioning

confidence: 99%

The Kidney Contains Ontogenetically Distinct Dendritic Cell and Macrophage Subtypes throughout Development That Differ in Their Inflammatory Properties

Salei

Rambichler

Salvermoser

et al. 2020

JASN

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“…Studies across both humans and mice have increasingly shown that cDCs and putative Axl + DCs can also be derived from both myeloid and lymphoid progenitors (89–91). This collectively reflects a paradigm shift in our understanding of haematopoiesis, moving away from a model of homogenous multipotent progenitors that bifurcate into distinct but rigid cell fates (i.e., MDP bifurcation into macrophage or dendritic cell fate) and instead toward one where lineage is imprinted early during development in early progenitors, possibly prior to the emergence of distinctive phenotypes (92–99).…”

Section: Dendritic Cell Subsets and Ontogenymentioning

confidence: 99%

Human Dendritic Cell Subsets, Ontogeny, and Impact on HIV Infection

et al. 2019

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Dendritic cells (DCs) play important roles in orchestrating host immunity against invading pathogens, representing one of the first responders to infection by mucosal invaders. From their discovery by Ralph Steinman in the 1970s followed shortly after with descriptions of their in vivo diversity and distribution by Derek Hart, we are still continuing to progressively elucidate the spectrum of DCs present in various anatomical compartments. With the power of high-dimensional approaches such as single-cell sequencing and multiparameter cytometry, recent studies have shed new light on the identities and functions of DC subtypes. Notable examples include the reclassification of plasmacytoid DCs as purely interferon-producing cells and re-evaluation of intestinal conventional DCs and macrophages as derived from monocyte precursors. Collectively, these observations have changed how we view these cells not only in steady-state immunity but also during disease and infection. In this review, we will discuss the current landscape of DCs and their ontogeny, and how this influences our understanding of their roles during HIV infection.

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“…This is also the case for the pre-cDCs, which already contain pre-cDC1, and pre-cDC2 (13, 14). In contrast, pDCs are also produced from a lymphoid progenitor (LP) (15) in the steady state whereas this happens for cDCs only in situation of cDC ablation (16).…”

Section: Introductionmentioning

confidence: 99%

What Makes a pDC: Recent Advances in Understanding Plasmacytoid DC Development and Heterogeneity

Musumeci¹,

Lutz²,

Winheim³

et al. 2019

Front. Immunol.

105

100

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Dendritic cells (DCs) are professional antigen presenting cells (APCs) that originate in the bone marrow and are continuously replenished from hematopoietic progenitor cells. Conventional DCs (cDCs) and plasmacytoid DCs (pDCs) are distinguished by morphology and function, and can be easily discriminated by surface marker expression, both in mouse and man. Classification of DCs based on their ontology takes into account their origin as well as their requirements for transcription factor (TF) expression. cDCs and pDCs of myeloid origin differentiate from a common DC progenitor (CDP) through committed pre-DC stages. pDCs have also been shown to originate from a lymphoid progenitor derived IL-7R + FLT3 + precursor population containing cells with pDC or B cell potential. Technological advancements in recent years have allowed unprecedented resolution in the analysis of cell states, down to the single cell level, providing valuable information on the commitment, and dynamics of differentiation of all DC subsets. However, the heterogeneity and functional diversification of pDCs still raises the question whether different ontogenies generate restricted pDC subsets, or fully differentiated pDCs retain plasticity in response to challenges. The emergence of novel techniques for the integration of high-resolution data in individual cells promises interesting discoveries regarding DC development and plasticity in the near future.

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Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo

Cited by 18 publications

References 89 publications

The Kidney Contains Ontogenetically Distinct Dendritic Cell and Macrophage Subtypes throughout Development That Differ in Their Inflammatory Properties

The Kidney Contains Ontogenetically Distinct Dendritic Cell and Macrophage Subtypes throughout Development That Differ in Their Inflammatory Properties

Human Dendritic Cell Subsets, Ontogeny, and Impact on HIV Infection

What Makes a pDC: Recent Advances in Understanding Plasmacytoid DC Development and Heterogeneity

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