Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CD1d orchestrates skin cell survival and inflammation in response to UV linking the etiology of sunburn to skin cancer

ABSTRACT: Solar UV represents a ubiquitous environmental physical insult. Thus, to maintain its integrity as an effective barrier, skin must be unusually resistant to cell death. However, UV overexposure causes sunburn1,2 (necrosis and inflammation) and cells that survive harbour damaged DNA, which if not repaired or removed by apoptosis can lead to skin cancer development3-10. CD1d, a transmembrane protein identified in glycolipid antigen presentation11,12 to invariant natural killer T (NKT) cells13,14 is expressed by epithelial cells of most tissues including skin15-17, and shares close homology between humans and mice12. Since CD1d and NKT cells are implicated in regulating UV skin carcinogenesis4,18, we studied susceptibility to UV-induced sunburn in mice either lacking expression of both CD1d and NKT cells or expressing CD1d without NKT cells. Here we show that CD1d, but not NKT cells is necessary for UV to cause sunburn. CD1d causes cells to resist apoptosis in response to UV overexposure as the means to promote cell survival and directs the expression of inflammatory response genes, resulting in tissue destruction and skin inflammation. This previously unknown action of CD1d links the etiology of sunburn to skin cancer. Keywords = CD1d knockout, UV, sunburn, cancer Keywords: other

ORGANISM(S): Mus musculus

PROVIDER: GSE2436 | GEO | 2016/11/27

SECONDARY ACCESSION(S): PRJNA91901

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Microarray screening of RNA samples from two human myeloma and two human lymphoma cell lines

Project description:This laboratory studies the T cell recognition of glycolipid antigens, including the biochemical characterization of glycolipid antigens, the cell biology of glycolipid antigen presenting machinery, the chemical synthesis of self and foreign glycolipids, and the cellular immunology that might shed light on finding glycolipid targets for adjuvant and vaccine development. In myeloid patients, the suppression of NKT cells has been reported. This suppression is mediated by endogenous glycolipid antigens presented by CD1d, a non-classic MHC molecule. Tumor B cells express CD1d molecule and preserve the capacity in presenting glycolipid antigens to NKT cells. However, the identity of the tumor glycolipid antigens remain unknown. We recently identified isoglobotrihexosylceramide (iGb3), as one endogenous ligand for human NKT cells. We have also purified iGb3 from thymuses of pediatric patients. Thus we hypothesize that iGb3 might be directly linked to the NKT suppression in myeloma patients. The processing of iGb3 requires the “assembly line” of glycosyltransferases, the glycosidases and sphingolipid activator proteins. The loading of iGb3 antigen is dependent on lipid transfer proteins such as saposins, and the more recently characterized CD1e molecule. Thus we used the Glyo-chip approach to have a systemic survey of the above enzyme and protein components. We hope to find clues to help us in understanding the glycolipid antigen presentation in tumor B cells. EXPERIMENT: We purified RNA from 2 myeloma cell lines (U226 and 8226) by the RNAqueous kit from Ambion, TX. RNA was also purified from 2 lymphoma cell lines (Daudi and RL). 4 samples were provided to Core E of Consortium of Functional Genomics for Glyco-chip version 2 array.

2011-03-02 | E-GEOD-27600 | biostudies-arrayexpress

NKT, CD1d-aGC+ Va24-, and CD4 T cell clones from human peripheral blood

Project description:Microarray analysis was performed to determine the transcriptional profiles of NKT, CD1d-aGC+ Va24-, and CD4 T cells. Clones of NKT, CD1d-aGC+ Va24-, and CD4 T cells were generated using peripheral blood drawn from two healthy individuals. RNA was extracted from cells that had been either rested (18 days post-stimulation) or stimulated (3 days post-stimulation).

2011-04-22 | E-GEOD-28726 | biostudies-arrayexpress

Microarray screening of RNA samples from two human myeloma and two human lymphoma cell lines

2011-03-02 | GSE27600 | GEO

Immunological Proteome Resource (ImmPRes): Liver derived CD4+ T cell proteomes

Project description:T cells play a critical role in liver immunity and take part both in the initiation and in the resolution of intrahepatic inflammation. The liver contains conventional CD4 T cells, and Natural Killer T (NKT) cells that express an invariant Vα14 T cell receptor that recognizes glycolipid/CD1d antigen complexes (iNKTs) and play a role in immune surveillance and immune homeostasis. ImmPRes includes a TMT based dataset characterising the proteomes of ex-vivo liver derived CD4+ T cells along with invariant NKT (iNKT) cells

2022-08-26 | PXD036319 | Pride

NKT, CD1d-aGC+ Va24-, and CD4 T cell clones from human peripheral blood

Project description:Microarray analysis was performed to determine the transcriptional profiles of NKT, CD1d-aGC+ Va24-, and CD4 T cells.

2011-04-22 | GSE28726 | GEO

RNA-seq of skin tissues from WT and Cd1d KO B6 mice

Project description:To investigate the effect of iNKT deficiency in the skin, the analysis of global gene expression in the skin tissues from WT and Cd1d KO mice were performed using RNA-seq data obtained from these samples.

2022-11-06 | GSE205602 | GEO

Expression data from CD1d tetramer-sorted b-GL122/LGL1âspecific human T cells or iNKT cells

Project description:The ability to detect and isolate bGL1-22/LGL1âspecific human type II NKT cells allowed us to compare the global gene expression profiles of these cells with type I NKT cells using microarray analysis. Principal component analysis revealed that the gene expression profile signature for bGL1-22 and LGL1-specific T cells both before and after activation with anti-CD3/CD28 beads is distinct from that of type I NKT cells. RNA from CD1d tetramer-sorted b-GL122/LGL1âspecific T cells or iNKT cells was amplified, labeled, and hybridized on the Affymetrix Human Genome U133 Plus 2.0 microarray chips. The data were analyzed with GeneSpring GX 12.5 (Agilent Technologies)

2016-02-16 | E-GEOD-77909 | biostudies-arrayexpress

Unveiling the heterogeneity of NKT cells in the liver through single cell RNA sequencing

Project description:CD1d-dependent type I NKT cells, which are activated by lipid antigen, are known to play important roles in innate and adaptive immunity, as are a portion of type II NKT cells. However, the heterogeneity of NKT cells, especially NKT-like cells, remains largely unknown. Here, we report the profiling of NKT (NK1.1+CD3e+) cells in livers from wild type (WT), Jα18-deficient and CD1d- deficient mice by single-cell RNA sequencing. Unbiased transcriptional clustering revealed distinct cell subsets. The transcriptomic profiles identified the well-known CD1d-dependent NKT cells and defined two CD1d-independent NKT cell subsets. In addition, validation of marker genes revealed the differential organ distribution and landscape of NKT cell subsets during liver tumor progression. More importantly, we found that CD1d-independent Sca-1−CD62L+ NKT cells showed a strong ability to secrete IFN-γ after costimulation with IL-2, IL-12 and IL-18 in vitro. Collectively, our findings provide a comprehensive characterization of NKT cell heterogeneity and unveil a previously undefined functional NKT cell subset.

2020-11-18 | GSE152962 | GEO

Sortase A-cleavable CD1d identifies sphingomyelins as major class of CD1d-associated lipids

Project description:CD1d is an atypical MHC class I molecule which binds endogenous and exogenous lipids and can activate natural killer T (NKT) cells through the presentation of lipid antigens. CD1d surveys different cellular compartments including the secretory and the endolysosomal pathway and broadly binds lipids through its two hydrophobic pockets. Purification of the transmembrane protein CD1d for the analysis of bound lipids is technically challenging as the use of detergents releases CD1d-bound lipids. To address these challenges, we have developed a novel approach based on Sortase A-dependent enzymatic release of CD1d at the cell surface of live mammalian cells, which allows for single step release and affinity tagging of CD1d for shotgun lipidomics. Using this system, we demonstrate that CD1d carrying the Sortase A recognition motif shows unimpaired subcellular trafficking through the secretory and endolysosomal pathway and is able to load lipids in these compartments and present them to NKT cells. Comprehensive shotgun lipidomics demonstrated that the spectrum and abundance of CD1d-associated lipids is not representative of the total cellular lipidome but rather characterized by preferential binding to long chain sphingolipids and glycerophospholipids. As such, sphingomyelin species recently identified as critical negative regulators of NKT cell activation, represented the vast majority of endogenous CD1d-associated lipids. Moreover, we observed that inhibition of endolysosomal trafficking of CD1d surprisingly did not affect the spectrum of CD1d-bound lipids, suggesting that the majority of endogenous CD1d-associated lipids load onto CD1d in the secretory rather than the endolysosomal pathway. In conclusion, we present a novel system for the analysis of CD1d-bound lipids in mammalian cells and provide new insight into the spectrum of CD1d-associated lipids, with important functional implications for NKT cell activation.

2022-06-13 | PXD034495 | panorama

SortaseA cleavable CD1d and H2Kb

Project description:Identification of SortaseA cleavable MHC class I proteins (CD1d, H2Kb) for shotgun lipidomics

2022-07-08 | PXD034366 | Pride