Filters
Technology
Platform
SRP148791
Mus musculus
17 Downloadable Samples
NextSeq 500
Description
Purpose: Controlling the balance between immunity and immunopathology is crucial for host resistance to pathogens. Upon infection, activation of the hypothalamic-pituitary-adrenal (HPA) axis leads to the production of glucocorticoids (GCs). However, the pleiotropic effects of these steroid hormones make it difficult to decipher their precise role in vivo. Our purpose was to study how GCs regulate the function of group 1 ILCs in spleen and liver upon Murine Cytomegalovirus (MCMV) infection. Methods: We studied the in vivo effect of endogenous GCs released upon MCMV infection on NK cells in spleen and liver and ILC1s in the liver. We compared WT mice with GRNcr1-iCre mice, in which the gene encoding for GC receptor (GR) is selectively deleted in Ncr1+ cells. Results: We found that the regulation of NK function by the GR is required for host protection against MCMV. Mechanistically, endogenous GCs produced shortly after infection induce the selective and tissue-specific expression of the immune checkpoint PD1 on NK cells. This GC-PD1 pathway mediates its immunoregulatory functions by limiting interferon (IFN)-g production by splenic NK cells, preventing lethal immunopathology. Importantly, this regulation does not compromise viral clearance. Conclusions:The fine-tuning of a selective subset of ILCs by the HPA axis preserves tissue integrity without impairing pathogen elimination, revealing a novel aspect of neuro-immune regulation. Overall design: Splenocytes (after NK cell enrichment with the mouse NK Cell Isolation Kit II, Miltenyi Biotec) and liver lymphocytes were pooled from three mice for each genotype. A FACS Aria III (BD Biosciences) was used to sort approximately 5 x 10^5 NK cells from the spleen and liver and 5 x 10^4 liver-resident ILC1s 44h post MCMV infection. We compared gene expression between glucocorticoid receptor (GR)-sufficient and deficient ILCs to identify the genes whose expression is regulated by GCs. Three biological replicates were generated for all samples except for the GRNcr1-iCre liver ILC1s sample (two biological replicates).
Publication Title
Endogenous glucocorticoids control host resistance to viral infection through the tissue-specific regulation of PD-1 expression on NK cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Caenorhabditis elegans
- 3 Downloadable Samples
Affymetrix C. elegans Gene 1.0 ST Array (elegene10st)
Description
The objective of this experiment was to determine changes in gene expression upon loss of alfa-1 in C.elegans under well-fed and starvation conditions. The human C9orf72 has an orthologue in C. elegans based on sequence homology, which is the F18A1.6 gene and also recently named as alfa-1 (ALS/FTD-associated gene homolog 1). We analyzed the domain structure of ALFA-1 and found that it shares the same DENN domains as human C9orf72, including the uDENN, cDENN, and dDENN domains. We obtained a mutant strain of the alfa-1 gene, which has a mutant allele (ok3062) of 486 bp deletion and 24 bp insertion in the region of exon 3 and exon 4. To understand the changes in gene expression in the alfa-1 mutant C. elegans, we performed the microarray gene expression profiling experiments under the defined conditions.
Publication Title
C9orf72/ALFA-1 controls TFEB/HLH-30-dependent metabolism through dynamic regulation of Rag GTPases.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
Homeostasis of the gut microbiota is pivotal to the survival of the host. Intestinal T cells and Innate Lymphoid cells (ILCs) control the composition of the microbiota and respond to its perturbations. Interleukin 22 (IL-22) plays a pivotal role in the immune control of gut commensal and pathogenic bacteria and is secreted by a heterogeneous population of intestinal T cells, NCR- ILC3 and NCR+ILC3. Expression of NCR by ILC3 is believed to define an irreversible effector ILC3 end-state fate in which these cells are key to control of bacterial infection via their production of IL-22. Here we identify the core transcriptional signature that drives the differentiation of NCR- ILC3 into NCR+ ILC3 and reveal that NCR+ILC3 exhibit more plasticity than originally thought, as NCR+ ILC3 can revert to NCR- ILC3. Contrary to the prevailing understanding of NCR+ ILC3 genesis and function, in vivo analyses of mice conditionally deleted of the key ILC3 genes Stat3, Il22, Tbet and Mcl1 demonstrated that NCR+ ILC3 were not essential for the control of colonic infections in the presence of T cells. However, NCR+ ILC3 were mandatory for homeostasis of the caecum. Our data identify that the interplay of intestinal T cells and ILC3 results in robust complementary fail-safe mechanisms that ensure gut homeostasis. Overall design: Transcriptional profiling of wild-type and T-bet knockout innate lymphoid cells (ILC3) using RNA sequencing
Publication Title
Complementarity and redundancy of IL-22-producing innate lymphoid cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This dataset was created to study M-CSF dependent in vitro differentiation of human monocytes to macrophages as a model process to demonstrate that independent component analysis (ICA) is a useful tool to support and extend knowledge-based strategies and to identify complex regulatory networks or novel regulatory candidate genes.
Publication Title
Analyzing M-CSF dependent monocyte/macrophage differentiation: expression modes and meta-modes derived from an independent component analysis.
Sample Metadata Fields
Specimen part
View Samples