Differentiation and function of mouse monocyte-derived dendritic cells in steady state and inflammation

2010 ◽  
Vol 234 (1) ◽  
pp. 90-104 ◽  
Author(s):  
Pilar M. Domínguez ◽  
Carlos Ardavín
Keyword(s):  
Dendritic Cells ◽  
Steady State ◽  
And Function

CXCR4 signaling controls dendritic cell location and activation at steady-state and in inflammation

Blood ◽  
2021 ◽  
Author(s):  
Carmen Gallego ◽  
Mathias Vétillard ◽  
Joseph Calmette ◽  
Mélanie Roriz ◽  
Viviana Marin-Esteban ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Steady State ◽  
Immune Responses ◽  
Chemokine Receptors ◽  
High Susceptibility ◽  
Cxcr4 Signaling ◽  
Whim Syndrome ◽  
Plasmacytoid Dcs ◽  
And Function ◽  
Specific Contribution

Dendritic cells (DCs) encompass several cell subsets that collaborate to initiate and regulate immune responses. Proper DC localization determines their function and requires the tightly controlled action of chemokine receptors. All DC subsets express CXCR4, but the genuine contribution of this receptor to their biology has been overlooked. We addressed this question using natural CXCR4 mutants resistant to CXCL12-induced desensitization and harboring a gain of function that cause the warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) Syndrome (WS), a rare immunodeficiency associated with high susceptibility to the pathogenesis of human papillomavirus (HPV). We report a reduction in the number of circulating plasmacytoid DCs (pDCs) in WHIM patients, whereas that of conventional DCs is preserved. This pattern was reproduced in an original mouse model of WS, enabling us to show that the circulating pDC defect can be corrected upon CXCR4 blockade and that pDC differentiation and function are preserved, despite CXCR4 dysfunction. We further identified proper CXCR4 signaling as a critical checkpoint for Langerhans-cell and DC migration from the skin to lymph nodes, with corollary alterations of their activation state and tissue inflammation in a model of HPV-induced dysplasia. Beyond providing new hypotheses to explain the susceptibility of WHIM patients to HPV pathogenesis, this study shows that proper CXCR4 signaling establishes a migration threshold that controls DC egress from CXCL12-containing environments and highlights the critical and subset-specific contribution of CXCR4 signal termination to DC biology.

scholarly journals The Dendritic Cell Lineage: Ontogeny and Function of Dendritic Cells and Their Subsets in the Steady State and the Inflamed Setting

2013 ◽  
Vol 31 (1) ◽  
pp. 563-604 ◽  
Author(s):  
Miriam Merad ◽  
Priyanka Sathe ◽  
Julie Helft ◽  
Jennifer Miller ◽  
Arthur Mortha
Keyword(s):  
Dendritic Cells ◽  
Steady State ◽  
Dendritic Cell ◽  
Cell Lineage ◽  
And Function

scholarly journals Development and function of human dendritic cells in humanized mice models

2020 ◽  
Vol 125 ◽  
pp. 151-161
Author(s):  
Giorgio Anselmi ◽  
Julie Helft ◽  
Pierre Guermonprez
Keyword(s):  
Dendritic Cells ◽  
Humanized Mice ◽  
And Function ◽  
Human Dendritic Cells

scholarly journals TLR2 and TLR4 as Potential Biomarkers of Environmental Particulate Matter Exposed Human Myeloid Dendritic Cells

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Marc A. Williams ◽  
Chris Cheadle ◽  
Tonya Watkins ◽  
Anitaben Tailor ◽  
Smruti Killedar ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Host Immunity ◽  
Tlr4 Expression ◽  
Myeloid Dendritic Cells ◽  
Critical Function ◽  
Danger Signals ◽  
Particulate Pollution ◽  
And Function ◽  
Biomarkers Of Effect ◽  
Potential Biomarkers

In many subjects who are genetically susceptible to asthma, exposure to environmental stimuli may exacerbate their condition. However, it is unknown how the expression and function of a family of pattern-recognition receptors called toll-like receptors (TLR) are affected by exposure to particulate pollution. TLRs serve a critical function in alerting the immune system of tissue damage or infection—the so-called “danger signals”. We are interested in the role that TLRs play in directing appropriate responses by innate immunity, particularly dendritic cells (DC), after exposing them to particulate pollution. Dendritic cells serve a pivotal role in directing host immunity. Thus, we hypothesized that alterations in TLR expression could be further explored as potential biomarkers of effect related to DC exposure to particulate pollution. We show some preliminary data that indicates that inhaled particulate pollution acts directly on DC by down-regulating TLR expression and altering the activation state of DC. While further studies are warranted, we suggest that alterations in TLR2 and TLR4 expression should be explored as potential biomarkers of DC exposure to environmental particulate pollution.

B lymphocytes can regulate the maturation and function of human dendritic cells but are partially inefficient in systemic lupus erythematosus

2012 ◽  
Vol 71 (Suppl 1) ◽  
pp. A34.1-A34
Author(s):  
Ahsen Morva ◽  
Sébastien Lemoine ◽  
Achouak Achour ◽  
Alain Saraux ◽  
Jacques-Olivier Pers ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dendritic Cells ◽  
B Lymphocytes ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
And Function ◽  
Human Dendritic Cells

scholarly journals NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5902
Author(s):  
Stefan Nagel ◽  
Claudia Pommerenke ◽  
Corinna Meyer ◽  
Hans G. Drexler
Keyword(s):  
Dendritic Cells ◽  
Transcription Factors ◽  
Cell Lines ◽  
Expression Profiling ◽  
Regulatory Network ◽  
Homeobox Gene ◽  
Leukemia Cell Line ◽  
Specific Gene ◽  
Rna Seq ◽  
And Function

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.

scholarly journals Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity

2005 ◽  
Vol 169 (4) ◽  
pp. 569-576 ◽  
Author(s):  
Clare L. Bennett ◽  
Erwin van Rijn ◽  
Steffen Jung ◽  
Kayo Inaba ◽  
Ralph M. Steinman ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Steady State ◽  
Diphtheria Toxin ◽  
Langerhans Cells ◽  
Contact Hypersensitivity ◽  
Relative Importance ◽  
Skin Immunity

Langerhans cells (LC) form a unique subset of dendritic cells (DC) in the epidermis but so far their in vivo functions in skin immunity and tolerance could not be determined, in particular in relation to dermal DC (dDC). Here, we exploit a novel diphtheria toxin (DT) receptor (DTR)/DT-based system to achieve inducible ablation of LC without affecting the skin environment. Within 24 h after intra-peritoneal injection of DT into Langerin-DTR mice LC are completely depleted from the epidermis and only begin to return 4 wk later. LC deletion occurs by apoptosis in the absence of inflammation and, in particular, the dDC compartment is not affected. In LC-depleted mice contact hypersensitivity (CHS) responses are significantly decreased, although ear swelling still occurs indicating that dDC can mediate CHS when necessary. Our results establish Langerin-DTR mice as a unique tool to study LC function in the steady state and to explore their relative importance compared with dDC in orchestrating skin immunity and tolerance.

scholarly journals Antibody Targeting of “Steady-State” Dendritic Cells Induces Tolerance Mediated by Regulatory T Cells

2016 ◽  
Vol 7 ◽  
Author(s):  
Karsten Mahnke ◽  
Sabine Ring ◽  
Alexander H. Enk
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Steady State ◽  
Regulatory T Cells ◽  
Antibody Targeting
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