IL-17A is a pro-inflammatory cytokine that promotes host defense against infections and contributes to the pathogenesis of chronic inflammatory diseases. Dendritic cells (DC) are antigen-presenting cells responsible for adaptive immune responses. Here, we report that IL-17A induces intense remodeling of lipid metabolism in human monocyte-derived DC, as revealed by microarrays analysis. In particular NR1H3/LXR-a and its target genes were significantly upregulated in response to IL-17A. IL-17A induced accumulation of Oil Red O-positive lipid droplets in DC leading to the generation of lipid-laden DC. A lipidomic study established that all the analyzed lipid species, i.e phospholipids, cholesterol, triglycerides, cholesteryl esters were elevated in IL-17A-treated DC. The increased expression of membrane lipid transporters in IL-17A-treated DC as well as their enhanced ability to uptake the fatty acid Bodipy-FL-C16 suggested that lipid uptake was the main mechanism responsible for lipid accumulation in response to IL-17A. IL-17A-induced lipid laden DC were able to stimulate allogeneic T cell proliferation in vitro as efficiently as untreated DC, indicating that IL-17A-treated DC are potently immunogenic. This study, encompassed in the field of immunometabolism, points out for the first time IL-17A as a modulator of lipid metabolism in DC and provides a rationale to delineate the importance of lipid-laden DC in IL-17A-related inflammatory diseases.
Human monocyte-derived dendritic cells turn into foamy dendritic cells with IL-17A.
Specimen part, Treatment
View SamplesThe adaptive mechanisms in response to excess energy supply are still poorly known in humans. Our aims were to define metabolic responses and changes in gene expression in adipose tissue of healthy volunteers during fat overfeeding.
Subcutaneous adipose tissue remodeling during the initial phase of weight gain induced by overfeeding in humans.
Specimen part, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Chronically dysregulated NOTCH1 interactome in the dentate gyrus after traumatic brain injury.
Sex, Specimen part, Treatment, Time
View SamplesThe macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation
Rapamycin-based graft-versus-host disease prophylaxis increases the immunosuppressivity of myeloid-derived suppressor cells without affecting T cells and anti-tumor cytotoxicity.
No sample metadata fields
View SamplesThe macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation. Recently, an activating effect of rapamycin on the function of myeloid-derived suppressor cells (MDSCs), a subset of immune suppressive cells of myeloid origin was reported. However, the effect of rapamycin treatment on MDSCs induction and function in the management of graft-versus-host disease is largely unknown.
Rapamycin-based graft-versus-host disease prophylaxis increases the immunosuppressivity of myeloid-derived suppressor cells without affecting T cells and anti-tumor cytotoxicity.
No sample metadata fields
View SamplesLong-term treatment of Kasumi-1 cells at clinically attained doses of dasatinib led to decreased drug-sensitivity by means of IC50 values (relative to treatment-naive cells). Changes were paralled by profound alterations in c-KIT expression and cell signaling signatures. Upon brief discontinuation of dasatinib treatment, these alterations reversed and drug sensitivity was restored.
Transitory dasatinib-resistant states in KIT(mut) t(8;21) acute myeloid leukemia cells correlate with altered KIT expression.
Cell line
View SamplesBackground: The diverse immunomodulatory effects of vitamin D are increasingly being recognized. However, the ability of oral vitamin D to modulate immune responses in vivo has not been established in humans. Methods: Twenty healthy adults were randomized to receive placebo or a single high dose of vitamin D3 (cholecalciferol) one hour after localized skin irradiation with an erythemogenic dose of ultraviolet radiation. Primary outcomes included skin redness, skin thickness, and tissue expression of inflammatory mediators (TNF- and iNOS). Secondary outcomes included microarray analyses. Results: As compared to placebo, subjects receiving vitamin D3 (200,000 IU) demonstrated reduced expression of TNF- (p=0.04) and iNOS (p=0.02) in skin biopsies 48 hours after ultraviolet light exposure. Demonstrated trends included reduced skin redness (p=0.17), and reduced skin thickness (p=0.09) in subjects receiving vitamin D3 (200,000 IU). Unsupervised clustering of individuals based on global gene expression revealed that subjects with enhanced skin barrier repair expression profiles had higher serum vitamin D3 levels (p=0.007), increased arginase expression (p=0.005), and a sustained reduction in skin redness (p=0.02) after treatment, as compared to subjects with enhanced inflammatory gene expression profiles.
Oral Vitamin D Rapidly Attenuates Inflammation from Sunburn: An Interventional Study.
Sex, Age, Specimen part, Race
View SamplesTo characterize LICs in ALL irrespective of surface markers expression, we investigated leukemia initiating activities of cellular subfractions of patient-derived xenograft BCP-ALL cells sorted according to different cell cycle phases (i.e. G0/G1 and G2/M) followed by transplantation onto NOD/SCID mice. All cell fractions led to leukemia engraftment indicating LIC activity irrespective of cell cycle stage. Most importantly, cells isolated from G0/G1 cell cycle phases led to early leukemia engraftment in contrast to cells from late cell cycle (G2/M). To further characterize cells with different engraftment potential in vivo, we analyzed the gene expression profiles of early (G1b early) and late (G2/M) engrafting cells.
Leukemia reconstitution <i>in vivo</i> is driven by cells in early cell cycle and low metabolic state.
Specimen part
View SamplesExpression profiling of progenitor cells from human supraclavicular and subcutaneous adipose tissue. Studies in animal models revealed that brown and white adipocytes derive from different progenitor cells. Molecular characteristics of these cells have not been investigated in detail in humans.
Comparative gene array analysis of progenitor cells from human paired deep neck and subcutaneous adipose tissue.
Sex, Age
View SamplesCNS leukemia is still the major obstacle in treating childhood acute lymphoblastic leukemia (ALL). We have used our NOD/SCID/huALL xenotransplantation model to identify molecular pathways leading to the infiltration of leukemic cells into the CNS compartment.
Central nervous system involvement in acute lymphoblastic leukemia is mediated by vascular endothelial growth factor.
No sample metadata fields
View Samples