We developed a method to convert gene expression signatures across the Illumina and Affymetrix platforms.
Cross-platform prediction of gene expression signatures.
Specimen part
View SamplesPurpose: 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).
Endogenous glucocorticoids control host resistance to viral infection through the tissue-specific regulation of PD-1 expression on NK cells.
Sex, Specimen part, Subject
View SamplesRetinoic acid (RA) is a potent inducer of cell differentiation and plays an essential role in sex-specific germ cell development in the mammalian gonad. RA is essential for male gametogenesis and hence fertility. However, RA can also disrupt sexual cell fate in somatic cells of the testis, promoting transdifferentiation of male Sertoli cells to female granulosa-like cells when the male sexual regulator Dmrt1 is absent. The feminizing ability of RA in the somatic testis suggests that RA might normally play a role in somatic cell differentiation or cell fate maintenance in the ovary. To test for this possibility we disrupted RA signaling in somatic cells of the early fetal ovary using three genetic strategies and one pharmaceutical approach. We found that deleting all three RA receptors (RARs) in the XX somatic gonad at the time of sex determination did not significantly affect ovarian differentiation, follicle development, or female fertility. Transcriptome analysis of adult triple mutant ovaries revealed remarkably little effect on gene expression in the absence of somatic RAR function. Likewise, deletion of three RA synthesis enzymes (Aldha1-3) at the time of sex determination did not masculinize the ovary. A dominant-negative RAR transgene altered granulosa cell proliferation, likely due to interference with a non-RA signaling pathway, but did not affect granulosa cell specification or fertility. Finally, culture of fetal XX gonads with an RAR antagonist blocked germ cell meiotic initiation but did not disrupt sex-biased gene expression. We conclude that RA signaling, although crucial in the ovary for meiotic initiation, is not required for granulosa cell specification, differentiation, or reproductive function. Overall design: Ovaries from six week old mice with five replicates in each of two genotypes were analyzed by RNA-Seq
Retinoic acid signaling is dispensable for somatic development and function in the mammalian ovary.
Age, Specimen part, Cell line, Subject
View SamplesPeyers patches (PP) are primary inductive sites of mucosal immunity. Defining PP mononuclear phagocyte system (MPS) is thus crucial to understand the initiation of mucosal immune response. We provide a comprehensive analysis of the phenotype, distribution,
Innate and adaptive immune functions of peyer's patch monocyte-derived cells.
Sex, Age, Specimen part
View SamplesNatural killer (NK) cells are NKp46+CD3- lymphocytes that can perform granule-dependent cytotoxicity and produce interferon-gamma, when isolated from blood, lymphoid organs, lung, liver and uterus. Here we identify in dermis, gut lamina propria and cryptopatches, very distinct populations of NKp46+CD3- cells with reduced ability to degranulate and to produce interferon-gamma. In gut, the transcription factor RORgamma-t and CD127 (IL-7R alpha) defined a novel subset of NKp46+CD3- that is reminiscent of lymphoid tissue inducer (LTi)-like cells. Gut ROR gamma t+NKp46+ cells produced IL-22 in contrast to ROR-gamma t-independent lamina propria and dermis NK cells. These data show that LTi-like cells and NK cells share unanticipated similarities and reveal the heterogeneity of NKp46+CD3- cells in innate immunity, lymphoid organization and local tissue repair.
Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin.
Sex, Age
View SamplesThe initiation of the mucosal immune response in Peyers patch (PP) relies on the sampling, processing and efficient presentation of foreign antigens by dendritic cells (DC). PP DC encompass five subsets, among which CD11b+ conventional DC (cDC) and LysoDC have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here, we have studied the genetic relatedness of the different subsets of PP cDC at steady state and under TLR7 ligand stimulation. We also provide the transcriptional profiles of subepithelial TIM-4- and interfollicular TIM-4+ macrophages.
Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation.
Sex, Age, Specimen part, Treatment
View SamplesSignatures of Oncogenic Pathway Deregulation in Human Cancers.
Oncogenic pathway signatures in human cancers as a guide to targeted therapies.
No sample metadata fields
View SamplesSignatures of Oncogenic Pathway Deregulation in Human Cancers.
Oncogenic pathway signatures in human cancers as a guide to targeted therapies.
No sample metadata fields
View SamplesSignatures of Oncogenic Pathway Deregulation in Human Cancers.
Oncogenic pathway signatures in human cancers as a guide to targeted therapies.
No sample metadata fields
View SamplesSignatures of Oncogenic Pathway Deregulation in Human Cancers
Oncogenic pathway signatures in human cancers as a guide to targeted therapies.
No sample metadata fields
View Samples