scholarly journals Integrated scRNA-seq analysis identifies conserved transcriptomic features of mononuclear phagocytes in mouse and human atherosclerosis

2020 ◽  
Author(s):  
Alma Zernecke ◽  
Florian Erhard ◽  
Tobias Weinberger ◽  
Christian Schulz ◽  
Klaus Ley ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Immune Cell ◽  
Expression Patterns ◽  
Coronary Vessels ◽  
Mononuclear Phagocytes ◽  
Cell Populations ◽  
Human Atherosclerosis ◽  
Macrophage Populations

AbstractRationaleAccumulation of mononuclear phagocytes (monocytes, macrophages and dendritic cells) in the vessel wall is a hallmark of atherosclerosis. Although single-cell RNA-sequencing (scRNA-seq) has shed new light on immune cell transcriptional diversity in atherosclerosis, it is still unknown whether the transcriptional states of mononuclear phagocytes are conserved between mouse and human atherosclerosis.ObjectiveTo integrate and compare macrophage and dendritic cell transcriptomes in mouse and human atherosclerosis.Methods and resultsWe integrated 12 scRNA-seq datasets of immune cells isolated from healthy or atherosclerotic mouse aortas, and scRNA-seq data from 11 patients (n=4 coronary vessels, n=7 carotid endarterectomy specimens) from two independent studies. Integration of mouse data recovered previously described macrophage populations and identified novel subpopulations with discrete transcriptomic signatures within populations of aortic resident (Lyve1), inflammatory (Il1b), as well as foamy (Trem2hi) macrophages. We identified unique transcriptomic features distinguishing aortic intimal resident macrophages from atherosclerosis-associated Trem2hi macrophages. Also, populations of Xcr1+ type 1 classical dendritic cells (cDC1), Cd209a+ cDC2 and mature DCs (Ccr7, Fscn1) were detected. In humans, we uncovered macrophage and dendritic cell populations with gene expression patterns similar to those observed in mice in both vascular beds. In particular, core transcripts of the foamy/Trem2hi signature (TREM2, SPP1, GPNMB, CD9) mapped to a specific population of macrophages in human lesions. Cross-species data integration demonstrated transcriptionally proximal macrophage and dendritic cell populations in mice and humans.ConclusionsWe demonstrate conserved transcriptomics features of macrophages and dendritic cells in atherosclerosis in mice and humans, emphasizing the relevance of mouse models to study mononuclear phagocytes in atherosclerosis.

scholarly journals Understanding the dendritic cell lineage through a study of cytokine receptors.

1994 ◽  
Vol 179 (6) ◽  
pp. 1767-1776 ◽  
Author(s):  
E Kämpgen ◽  
F Koch ◽  
C Heufler ◽  
A Eggert ◽  
L L Gill ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Binding Sites ◽  
Cell Lineage ◽  
Mononuclear Phagocytes ◽  
Cytokine Receptors ◽  
Gm Csf ◽  
High Affinity ◽  
Epidermal Dendritic Cells

Dendritic cells form a system of antigen presenting cells that are specialized to stimulate T lymphocytes, including quiescent T cells. The lineage of dendritic cells is not fully characterized, although prior studies have shown that growth and differentiation are controlled by cytokines, particularly granulocyte/macrophage colony-stimulating factor (GM-CSF). To further elucidate the nature and control of the dendritic cell lineage, we have studied the expression of specific cytokine receptors. Sufficient numbers of dendritic cells were purified from spleen and skin to do quantitative binding studies with radiolabeled M-CSF, GM-CSF, and interleukin 1 (IL-1). To verify the nonlymphoid nature of dendritic cells, we made an initial search for rearrangements in T cell receptor and immunoglobulin genes and none were found. M-CSF binding sites, a property of mononuclear phagocytes, also were absent. In contrast, GM-CSF receptors were abundant on mature dendritic cells, with approximately 3,000 binding sites/cell with a single Kd of 500-1,000 pM. Substantial numbers of high affinity (< 100 pM) IL-1 binding sites were identified as well; cultured epidermal dendritic cells (i.e., epidermal Langerhans cells) had 500/cell and spleen dendritic cells approximately 70/cell. Cross-linking approaches showed the 80-kD species that is expected of high-affinity type 1 IL-1 receptor. Anti-type 1 IL-1 receptor (R) mAbs also visualized these receptors by flow cytometry on freshly isolated epidermal dendritic cells. These results provide new evidence that dendritic cells represent a differentiation pathway distinct from lymphocytes and monocytes. Together with recent findings on the effects of IL-1 and GM-CSF on epidermal dendritic cells in situ (see Results and Discussion), the data lead to a proposal whereby IL-1 signals IL-1R to upregulate GM-CSF receptors and thereby, the observed responsiveness of dendritic cells to GM-CSF for growth, viability, and function.

scholarly journals Restricted Clonal Expression of IL-2 By Naive T Cells Reflects Differential Dynamic Interactions with Dendritic Cells

2003 ◽  
Vol 198 (1) ◽  
pp. 123-132 ◽  
Author(s):  
Vincent Hurez ◽  
Arman Saparov ◽  
Albert Tousson ◽  
Michael J. Fuller ◽  
Takekazu Kubo ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Gene Transcription ◽  
Cell Populations ◽  
Intrinsic Variability ◽  
Dynamic Interactions ◽  
Transgenic Model ◽  
Transient Interactions

Limited frequencies of T cells express IL-2 in primary antigenic responses, despite activation marker expression and proliferation by most clonal members. To define the basis for restricted IL-2 expression, a videomicroscopic system and IL-2 reporter transgenic model were used to characterize dendritic cell (DC)–T cell interactions. T cells destined to produce IL-2 required prolonged interactions with DCs, whereas most T cells established only transient interactions with DCs and were activated, but did not express IL-2. Extended conjugation of T cells with DCs was not always sufficient to initiate IL-2 expression. Thus, there is intrinsic variability in clonal T cell populations that restricts IL-2 commitment, and prolonged engagement with mature DCs is necessary, but not sufficient, for IL-2 gene transcription.

DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin) and DC-SIGN-related (DC-SIGNR): friend or foe?

2003 ◽  
Vol 104 (4) ◽  
pp. 437-446 ◽  
Author(s):  
Elizabeth J. SOILLEUX
Keyword(s):  
Endothelial Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
T Lymphocytes ◽  
High Efficiency ◽  
Immunoglobulin E ◽  
Expression Patterns ◽  
Intercellular Adhesion Molecule ◽  
Carbohydrate Binding ◽  
Wide Range

C-type lectins are calcium-dependent carbohydrate-binding proteins with a wide range of biological functions, many of which are related to immunity. DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin, where ICAM is intercellular adhesion molecule) is a recently described mannose-specific C-type lectin expressed by dendritic cells. Dendritic cells are potent antigen-presenting cells capable of activating T-lymphocytes. DC-SIGN, which is expressed by dendritic cells, binds to ICAM-3 on T-lymphocytes, therefore playing an important role in the activation of T-lymphocytes. DC-SIGN can also bind HIV, and the virus may remain bound to DC-SIGN for protracted periods. DC-SIGN may deliver bound HIV to permissive cell types, mediating infection with high efficiency. A closely related C-type lectin, DC-SIGN-related molecule (DC-SIGNR) has also been described. DC-SIGNR is expressed by restricted subsets of endothelial cells, but has similar ICAM-3 and HIV-binding properties to DC-SIGN. This review describes the mapping of DC-SIGN and DC-SIGNR to chromosome 19p13.3 adjacent to the previously described C-type lectin, CD23 [the low-affinity receptor for immunoglobulin E (FcERII)]. The similar genomic organization of these three genes is discussed and consideration is given to the evolutionary duplications that may underlie this arrangement. Both DC-SIGN and DC-SIGNR possess a neck region, made up of multiple repeats, which supports the ligand-binding domain. Consideration is given to the biological reasons underlying the considerable polymorphism in the numbers of repeats in DC-SIGNR, but not DC-SIGN. The expression patterns of both DC-SIGN and DC-SIGNR are discussed in detail, with particular attention to the expression of both molecules in the placenta, which may have implications for the vertical transmission of HIV. Since dendritic cells may be important in determining the phenotype of many immune responses, via effects on T-lymphocytes, the differential expression of DC-SIGN by particular dendritic cell subsets may have important implications for the immunobiological functions of DC-SIGN. Similarly, the expression of DC-SIGNR by very restricted subsets of endothelial cells may give clues to the function of DC-SIGNR. Finally, the role of DC-SIGN in pathology, particularly in infective and neoplastic processes, is discussed, followed by speculation about likely future developments in this field.

Development of thymic and splenic dendritic cell populations from different hemopoietic precursors

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3376-3382 ◽  
Author(s):  
Li Wu ◽  
Angela D'Amico ◽  
Hubertus Hochrein ◽  
Meredith O'Keeffe ◽  
Ken Shortman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Cell Populations ◽  
Lymphoid Tissues ◽  
Hemopoietic Precursors ◽  
Surface Molecules ◽  
Splenic Dendritic Cell ◽  
Antigen Presenting ◽  
Macrophage Precursors

Abstract The antigen-presenting dendritic cells (DCs) found in mouse lymphoid tissues are heterogeneous. Several types of DCs have been identified on the basis of the expression of different surface molecules, including CD4, CD8α, and DEC-205. Previous studies by the authors showed that the mouse intrathymic lymphoid-restricted precursors (lin−c-kit+Thy-1lowCD4low) can produce DCs in the thymus and spleen upon intravenous transfer, suggesting a lymphoid origin of these DCs. In the current study, the potential for DC production by the newly identified bone marrow (BM) common lymphoid precursors (CLPs), common myeloid precursors (CMPs), and committed granulocyte and macrophage precursors was examined. It was found that both the lymphoid and the myeloid precursors had the potential to produce DCs. All the different DC populations identified in mouse thymus and spleen could be produced by all these precursor populations. However, CLPs produced predominantly the CD4−CD8α+ DCs, whereas CMPs produced similar numbers of CD4−CD8α+ and CD4+CD8α− DCs, although at different peak times. On a per cell basis, the CLPs were more potent than the CMPs at DC production, but this may have been compensated for by an excess of CMPs over CLPs in BM. Overall, this study shows that the expression of CD8α does not delineate the hemopoietic precursor origin of DCs, and the nature of the early precursors may bias but does not dictate the phenotype of the DC product.

scholarly journals Cannabinoid type 2 receptor (CB2R) distribution in dermatomyositis skin and peripheral blood mononuclear cells (PBMCs) and in vivo effects of LenabasumTM

2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Spandana Maddukuri ◽  
Jay Patel ◽  
De Anna Diaz ◽  
Kristen L. Chen ◽  
Maria Wysocka ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Immune Cell ◽  
Cell Populations ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

Abstract Background Lenabasum is a cannabinoid type 2 receptor (CB2R) reverse agonist that demonstrates anti-inflammatory effects in vivo and in vitro in dermatomyositis (DM) and is currently being investigated for therapeutic potential. The purpose of our study is to investigate CB2R distribution as well as the effects of lenabasum in DM. Methods Immunohistochemistry staining (IHC) was utilized to examine immune cell and cytokine production changes in lesional DM skin biopsies from lenabasum and placebo-treated patients. CB2R expression in various immune cell populations within DM skin was investigated with image mass cytometry (IMC), whereas flow cytometry elucidated CB2R expression in DM peripheral blood mononuclear cells (PBMCs) as well as cytokine production by CB2R-expressing cell populations. Results After 12 weeks of lenabasum treatment, IHC staining showed that CD4+ T cells, CB2R, IL-31, IFN-γ, and IFN-β cytokines were downregulated. IFN-γ and IFN-β mRNA decreased in lesional DM skin but not in PBMCs. IMC findings revealed that CB2R was upregulated in DM lesional skin compared to HC skin and DM PBMCs (p<0.05). In DM skin, CB2R was upregulated on dendritic cells, B cells, T cells, and macrophages while dendritic cells had the greatest expression in both DM skin and PBMCs (p<0.05). These CB2R+ cells in the skin produce IL-31, IL-4, IFN-γ, and IFN-β. Conclusion Our findings of differential CB2R expression based on location and cell type suggest modes by which lenabasum may exert anti-inflammatory effects in DM and highlights dendritic cells as potential therapeutic targets.

scholarly journals Regulation of Intestinal Dendritic Cell Migration and Activation by Plasmacytoid Dendritic Cells, TNF-α and Type 1 IFNs after Feeding a TLR7/8 Ligand

2006 ◽  
Vol 176 (9) ◽  
pp. 5205-5212 ◽  
Author(s):  
Ulf Yrlid ◽  
Simon W. F. Milling ◽  
Joanna L. Miller ◽  
Sian Cartland ◽  
Christopher D. Jenkins ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Migration ◽  
Dendritic Cell ◽  
Plasmacytoid Dendritic Cells ◽  
Tnf Α ◽  
Dendritic Cell Migration

Type-1 polarized nature of mouse liver CD8α and CD8α+ dendritic cells: tissue-dependent differences offset CD8α-related dendritic cell heterogeneity

2003 ◽  
Vol 33 (7) ◽  
pp. 2007-2013 ◽  
Author(s):  
Peta J. O'Connell ◽  
Young-Ik Son ◽  
Adam Giermasz ◽  
Zhiliang Wang ◽  
Alison J. Logar ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Mouse Liver ◽  
Cell Heterogeneity

scholarly journals Dendritic Cell Populations in Leishmania major-Infected Skin and Draining Lymph Nodes

2004 ◽  
Vol 72 (4) ◽  
pp. 1991-2001 ◽  
Author(s):  
Tracey Baldwin ◽  
Sandrine Henri ◽  
Joan Curtis ◽  
Meredith O'Keeffe ◽  
David Vremec ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Lymph Nodes ◽  
Leishmania Major ◽  
Mouse Skin ◽  
Parasite Load ◽  
Plasmacytoid Dendritic Cells ◽  
Cell Populations ◽  
Infection Model ◽  
Draining Lymph Nodes

ABSTRACT Using a metacyclic promastigote ear infection model of cutaneous leishmaniasis, we examined the phenotype, parasite load, and cytokine production of dendritic cells in the skin and draining lymph nodes of resistant C57BL/6J and susceptible BALB/c mice. Five dendritic cell populations were isolated from the skin and lymph nodes, and the main difference between the groups of mice was an increased number of plasmacytoid dendritic cells in the lymph nodes of the susceptible mice. Although similar cell types were present in the skin emigrants of both strains, there was a 10-fold larger number of cells in BALB/c mouse skin early in infection than in C57BL/6J mouse skin. None of the dendritic cells in the lymph nodes harbored parasites until 3 weeks after infection, with the Langerhans cells having the largest load and the plasmacytoid dendritic cells having the smallest load but the longest lasting infection. Although parasites could be detected in the lymph nodes a few hours after infection, none of the skin emigrants harbored parasites, indicating that they are not the vehicle that ferries the parasites from the skin to the lymph nodes. The presence of larger numbers of plasmacytoid cells in infected BALB/c mice, the more protracted infection of these cells, and their production of alpha interferon point to a complex and important role for the plasmacytoid cells in leishmaniasis.

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