scholarly journals Mouse conventional dendritic cells can be universally classified based on the mutually exclusive expression of XCR1 and SIRPα

2014 ◽  
Author(s):  
Stephanie Gurka ◽  
Evelyn Hartung ◽  
Martina Becker ◽  
Richard A. Kroczek

Since the identification of mouse dendritic cells (DC) in the early 70s, all attempts to consistently classify the identified functional DC subpopulations according to their surface molecule expression failed. In the absence of DC lineage markers, a great variety of non-congruent surface molecules were used instead. Recently advances in the understanding of the involvement of transcription factors in the differentiation of DC subpopulations, together with the identification of a lineage marker for cross-presenting DC, has now allowed to establish a consistent and unified DC classification in the mouse. We demonstrate in the present article that all conventional DC in the mouse can be universally subdivided into either XCR1+ cross-presenting DC or SIRPα+ DC, irrespective of their activation status. This advancement will greatly facilitate future work on the biology of mouse DC. We discuss this new classification in view of current DC classification systems in the mouse and the human.

2021 ◽  
Vol 22 (11) ◽  
pp. 5902
Author(s):  
Stefan Nagel ◽  
Claudia Pommerenke ◽  
Corinna Meyer ◽  
Hans G. Drexler

Recently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Analysis of public gene expression profiling and RNA-seq datasets containing plasmacytoid and conventional dendritic cells (pDC and cDC) demonstrated HHEX activity in both entities while cDCs additionally expressed VENTX. The consequent aim of our study was to examine regulation and function of VENTX in DCs. We compared profiling data of VENTX-positive cDC and monocytes with VENTX-negative pDC and common myeloid progenitor entities and revealed several differentially expressed genes encoding transcription factors and pathway components, representing potential VENTX regulators. Screening of RNA-seq data for 100 leukemia/lymphoma cell lines identified prominent VENTX expression in an acute myelomonocytic leukemia cell line, MUTZ-3 containing inv(3)(q21q26) and t(12;22)(p13;q11) and representing a model for DC differentiation studies. Furthermore, extended gene analyses indicated that MUTZ-3 is associated with the subtype cDC2. In addition to analysis of public chromatin immune-precipitation data, subsequent knockdown experiments and modulations of signaling pathways in MUTZ-3 and control cell lines confirmed identified candidate transcription factors CEBPB, ETV6, EVI1, GATA2, IRF2, MN1, SPIB, and SPI1 and the CSF-, NOTCH-, and TNFa-pathways as VENTX regulators. Live-cell imaging analyses of MUTZ-3 cells treated for VENTX knockdown excluded impacts on apoptosis or induced alteration of differentiation-associated cell morphology. In contrast, target gene analysis performed by expression profiling of knockdown-treated MUTZ-3 cells revealed VENTX-mediated activation of several cDC-specific genes including CSFR1, EGR2, and MIR10A and inhibition of pDC-specific genes like RUNX2. Taken together, we added NKL homeobox gene activities for progenitor-derived DCs to the NKL-code, showing that VENTX is expressed in cDCs but not in pDCs and forms part of a cDC-specific gene regulatory network operating in DC differentiation and function.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Stephan Hailfinger ◽  
Klaus Schulze-Osthoff

Abstract Psoriasis is a frequent autoimmune-related skin disease, which involves various cell types such as T cells, keratinocytes and dendritic cells. Genetic variations, such as mutations of CARD14, can promote the development of the disease. CARD14 mutations as well as the stimulation of immune and cytokine receptors activate the paracaspase MALT1, a potent activator of the transcription factors NF-κB and AP-1. The disease-promoting role of MALT1 for psoriasis is mediated by both its protease activity as well as its molecular scaffold function. Here, we review the importance of MALT1-mediated signaling and its therapeutic implications in psoriasis.


Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2852-2857 ◽  
Author(s):  
Isabel Ferrero ◽  
Werner Held ◽  
Anne Wilson ◽  
Fabienne Tacchini-Cottier ◽  
Freddy Radtke ◽  
...  

The developmental origin of dendritic cells (DCs) is controversial. In the mouse CD8α+ and CD8α− DC subsets are often considered to be of lymphoid and myeloid origin respectively, although evidence on this point is conflicting. Very recently a novel CD11c+ B220+ DC subset has been identified that appears to be the murine counterpart to interferon alpha (IFNα)–producing human plasmacytoid DCs (PDCs). We show here that CD11c+ B220+ mouse PDCs, like human PDCs, are present in the thymus and express T lineage markers such as CD8α and CD4. However, the intrathymic development of PDCs can be completely dissociated from immature T lineage cells in mixed chimeras established with bone marrow cells from mice deficient for either Notch-1 or T-cell factor 1, two independent mutations that severely block early T-cell development. Our data indicate that thymic PDCs do not arise from a bipotential T/DC precursor.


2018 ◽  
Vol 6 (4) ◽  
pp. 88 ◽  
Author(s):  
Sandra Solano-Gálvez ◽  
Sonia Tovar-Torres ◽  
María Tron-Gómez ◽  
Ariane Weiser-Smeke ◽  
Diego Álvarez-Hernández ◽  
...  

Dendritic cells (DCs) are a type of cells derived from bone marrow that represent 1% or less of the total hematopoietic cells of any lymphoid organ or of the total cell count of the blood or epithelia. Dendritic cells comprise a heterogeneous population of cells localized in different tissues where they act as sentinels continuously capturing antigens to present them to T cells. Dendritic cells are uniquely capable of attracting and activating naïve CD4+ and CD8+ T cells to initiate and modulate primary immune responses. They have the ability to coordinate tolerance or immunity depending on their activation status, which is why they are also considered as the orchestrating cells of the immune response. The purpose of this review is to provide a general overview of the current knowledge on ontogeny and subsets of human dendritic cells as well as their function and different biological roles.


2020 ◽  
Vol 46 (2) ◽  
pp. 93-99 ◽  
Author(s):  
Ali Tunkiwala ◽  
Udatta Kher ◽  
Nupur H. Vaidya

A thorough and precise treatment plan that considers various factors such as age, availability of bone, interarch space for prosthesis design, smile line, lip support, patient desires, and economics is a necessity before implant surgery. Many previous classification systems for treatment planning in edentulous situations tend to focus on only a certain parameter such as esthetics, or available bone volume, or are specifically designed for the maxilla or mandible. The authors have proposed a simplified and universal ABCD classification that uses the 4 vital parameters of age, bone volume, cosmetic display, and degree of resorption to create an algorithm that satisfies the treatment needs of every patient. Various permutations of the 4 parameters can be used to arrive at a solution that streamlines the further phases of the rehabilitative process. The aim of the present article is to provide a science-driven approach to understand a patient's individual needs with careful attention to the interplay of all the aforementioned factors in the decision-making process.


Cephalalgia ◽  
2017 ◽  
Vol 37 (7) ◽  
pp. 609-612 ◽  
Author(s):  
Peter Svensson ◽  
Arne May

It is indisputable that the global scientific advances in headache research, be it bench or bedside, have benefited enormously from the operational diagnostic criteria published in 1988. Today, this classification system is indispensable. The reason for this success is a low inter-rater variability. In general, orofacial pain conditions are less well characterised – with the noticeable exemption of temporomandibular disorder pain. Tremendous work has been put into changing this, and significant progress has been achieved – in particular, in terms of the clinical implications and overriding conceptual models for oro-facial pain. Scientific classifications have only one goal: To provide a scientific agreement about the main features of an object of research and a scientific consensus regarding the name. The main significance is not the fact that a good classification offers a detailed and accurate image of the reality. If we want to overcome the obstacles of different competing classification systems, we need to overcome specialisation borders. The key to success is to understand that such a definition does not mirror all possible clinical facets of a given pain condition but is simply a convention – that is, a consensus on a word used for a pain condition. Simply speaking, a classification creates a common language to be used by more than one profession. It will be crucial to define any given pain condition as precisely and rigid as possible, in order to ensure a homogenous population. Only this ensures a low inter-rater variability, which consequently allows combining and comparing research on a population across different professional settings. This is not easy for chronic facial pain without verifiable morphological cause or structural lesions, as these syndromes are often rather featureless. The new IASP classification of chronic pain is a big step forward to a better characterisation of such conditions, and will trigger future work on a new and operationalised classification of oro-facial pain.


Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3376-3382 ◽  
Author(s):  
Li Wu ◽  
Angela D'Amico ◽  
Hubertus Hochrein ◽  
Meredith O'Keeffe ◽  
Ken Shortman ◽  
...  

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.


2011 ◽  
Vol 208 (8) ◽  
pp. 1695-1705 ◽  
Author(s):  
Niroshana Anandasabapathy ◽  
Gabriel D. Victora ◽  
Matthew Meredith ◽  
Rachel Feder ◽  
Baojun Dong ◽  
...  

Antigen-presenting cells in the disease-free brain have been identified primarily by expression of antigens such as CD11b, CD11c, and MHC II, which can be shared by dendritic cells (DCs), microglia, and monocytes. In this study, starting with the criterion of Flt3 (FMS-like receptor tyrosine kinase 3)-dependent development, we characterize the features of authentic DCs within the meninges and choroid plexus in healthy mouse brains. Analyses of morphology, gene expression, and antigen-presenting function established a close relationship between meningeal and choroid plexus DCs (m/chDCs) and spleen DCs. DCs in both sites shared an intrinsic requirement for Flt3 ligand. Microarrays revealed differences in expression of transcripts encoding surface molecules, transcription factors, pattern recognition receptors, and other genes in m/chDCs compared with monocytes and microglia. Migrating pre-DC progenitors from bone marrow gave rise to m/chDCs that had a 5–7-d half-life. In contrast to microglia, DCs actively present self-antigens and stimulate T cells. Therefore, the meninges and choroid plexus of a steady-state brain contain DCs that derive from local precursors and exhibit a differentiation and antigen-presenting program similar to spleen DCs and distinct from microglia.


1996 ◽  
Vol 44 (10) ◽  
pp. 1115-1122 ◽  
Author(s):  
S R Hasslen ◽  
A R Burns ◽  
S I Simon ◽  
C W Smith ◽  
K Starr ◽  
...  

We used transmission and scanning electron microscopy in conjunction with immunogold labeling to study cell surface molecules for evidence of distribution-function relationships. Ascription of functional significance to surface distribution therefore requires preservation of cell morphology and maintenance of molecular expression and distribution through the multiple steps of cell preparation. These requirements prompted us to compare two methods for preparing leukocytes for analysis of surface molecule distribution: one method involved using low temperature to "stabilize" cell morphology and surface molecular organization through immunolabeling; the other involved fixation of the cells with dilute glutaraldehyde before their isolation and labeling. Binding of primary antibodies to several surface molecules, measured by flow cytometry, was comparable for cells prepared by the two methods. Cell morphology and molecular distributions, assessed by high-resolution field emission SEM, were likewise comparable. These results support the conclusion that cell morphologies and CAM distributions previously reported were not affected by exposure of the cells to low temperature through isolation and immunolabeling. Our additional observation that Thy-1 is expressed on both non-projecting and projecting membrane domains of mouse lymph node lymphocytes and rat thymocytes represents a third and new pattern of surface molecule distribution.


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