Similar Datasets
Project description:ATAC-seq of bone marrow ILC2 lineages and Lung ILC2 steady state
| PRJNA902402 | ENA
Project description:Group 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2 reside within complex microenvironments where they are subject to cues from both the diet and invading pathogens – including helminths. Emerging evidence suggests ILC2 are acutely sensitive not only to canonical activating signals, but also perturbations in nutrient availability. In the context of helminth infection, we identify amino acid availability as a nutritional cue in regulating ILC2 responses. ILC2 were found to be uniquely pre-primed to import amino acids via the large neutral amino acid transporters Slc7a5 and Slc7a8. Cell-intrinsic deletion of these transporters individually impaired ILC2 expansion, while concurrent loss of both transporters markedly impaired the proliferative and cytokine producing capacity of ILC2. Moreover, amino acid determined the magnitude of ILC2 responses in part via tuning of mTOR. These findings implicate essential amino acids as a metabolic requisite for optimal ILC2 responses within mucosal barrier tissues.
2022-12-22 | PXD038792 | Pride
Project description:The ETS1 transcription factor is required for the development and cytokine-induced expansion of ILC2 ILC2 cells isolated from ETS1-deleted or litter mate control mice were cultured on OP9-DL1 with IL-7 and IL-33. Subsequently, RNA from ICOS+ cells was extracted, labelled and hybridized to Affymetrix microarrays. The goal of this study is to investigate ETS1-dependent genes in developing ILC2 cells.
2016-04-01 | E-GEOD-79742 | biostudies-arrayexpress
Project description:ILC2 cells are a newly described cell type whose biology and contribution to disease are poorly understood. ILC2 cells are activated by allergens, viral infection, and/or epithelial damage via IL-33 and IL-25. ILC2 cells require IL-2, IL-7, IL-25 and IL-33 for their survival and expansion. In mice, ILC2s produce multiple mediators primarily associated with type 2 inflammation (IL-13, IL-5, IL-4, IL-6, IL-9, IL-10, GM-CSF, amphiregulin). ILC2 cells may contribute to the pathology of asthma through multiple mediators that include IL-13-independent pathways. Our goal is to compare transcriptional profiles of IL-33- or IL-25-activated ILC2 cells from blood to characterize these cells and to identify marker(s) that can be utilized to detect them in human tissue. ILC2 cells (Lineage negative, CRTH2+, CD161+, CD127+) were purified from human blood of 5 different donors by flow cytometry. The ILC2 yield ranged from 20,000 to 165,000 cells per donor (0.001-0.008% WBC). Purified ILC2s were expanded in vitro in the presence of IL-2, IL-7, IL-33 and IL-25 (each at 50 ng/ml) for 7-10 days. Expanded cells maintained the ILC2 phenotype (Lineage negative, CRTH2+, CD161+, CD127+). The cells were rested for 2 days in the presence of 1 ng/ml IL-2 and IL-7 and then treated in the presence of 1 ng/ml IL-2 and IL-7 with either media control, IL-25 (50 ng/ml), IL-33 (50 ng/ml), and/or TSLP (50 ng/ml) in combination, for 6 or 24 hours. Whole RNA was isolated via the RNeasy kit (Qiagen). Stratagene Universal Human Reference RNA was used as the reference.
2013-12-31 | E-GEOD-45458 | biostudies-arrayexpress
Project description:Group 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2 reside within complex microenvironments where they are subject to cues from both the diet and invading pathogens – including helminths. Emerging evidence suggests ILC2 are acutely sensitive not only to canonical activating signals, but also perturbations in nutrient availability. In the context of helminth infection, we identify amino acid availability as a nutritional cue in regulating ILC2 responses. ILC2 were found to be uniquely pre-primed to import amino acids via the large neutral amino acid transporters Slc7a5 and Slc7a8. Cell-intrinsic deletion of these transporters individually impaired ILC2 expansion, while concurrent loss of both transporters markedly impaired the proliferative and cytokine producing capacity of ILC2. Moreover, amino acid determined the magnitude of ILC2 responses in part via tuning of mTOR. These findings implicate essential amino acids as a metabolic requisite for optimal ILC2 responses within mucosal barrier tissues.
2022-12-22 | PXD038786 | Pride
Project description:Innate lymphoid cells (ILCs) are critical mediators of immune responses by their robust production of cytokines. ILCs are mainly present in mucosal tissues, but their regulatory function in the kidney is attracting attention. Nevertheless, the understanding of their unique biology, compared to other tissues, is largely unknown.Here, we aimed to examine the effect of BALB/c and C57BL/6 strains on the number and function of kidney ILCs and their underlying mechanisms. Although the BALB/c strain showed an increase in ILC2 frequency than that of C57BL/6 in most organs, the difference in ILC2 frequency between the two strains was most pronounced in the kidney. These results were derived from increased ILC precursors in the bone marrow, and levels of renal Il2 in BALB/c mice. Furthermore, IL-2 receptor (CD25) expression and STAT5 phosphorylation also exaggerated in BALB/c kidney ILC2s. However, similar IL-2-dependent proliferation and activation of ILC2s were observed upon IL-2C treatment in both strains. Thus, homeostatic differences in kidney ILC2 number and function derive from differences in IL-2 signaling resulting from intrinsic and extrinsic factors. Together, we demonstrate previously unknown properties of kidney ILC2s based on their mice strain background and contributing factors. All these factors should be considered critical for the successful translation of immune diseases in experimental mouse models.
2023-01-31 | GSE208404 | GEO
Project description:ObjectiveFaster engraftment of G-CSF-mobilized peripheral blood (MPB) transplants compared to steady-state bone marrow (ssBM) is well documented and clinically relevant. A number of different factors likely contribute to this outcome. In the present study we explored whether independent of cell number there are intrinsic differences in the efficiency of progenitor cell homing to marrow between MPB and ssBM.MethodsMobilization was achieved by continuous infusion of G-CSF alone or in combination with other mobilizing agents. In vivo homing assays, in vitro migration assays, gene expression analysis, and flow cytometry were utilized to compare homing-related in vivo and in vitro properties of MPB and ssBM HPC.ResultsMarrow homing of murine MPB HPC, generated by different mobilizing schemes, was reproducibly significantly superior to that of ssBM, in lethally irradiated as well as in nonirradiated hosts. This phenotype was independent of MMP9, selectins, and beta2- and alpha4-integrins. Superior homing was also observed for human MPB HPC transplanted into NOD/SCIDbeta2microglobulin(-/-) recipients. Inhibition of HPC migration abrogated the homing advantage of MPB but did not affect homing of ssBM HPC, whereas enhancement of motility by CD26 inhibition improved marrow homing only of ssBM HPC. Enhanced SDF-1-dependent chemotaxis and low CD26 expression on MPB HPC were identified as potential contributing factors. Significant contributions of the putative alternative SDF-1 receptor, RDC1, were unlikely based on gene expression data.ConclusionThe data suggest increased motility as a converging endpoint of complex changes seen in MPB HPC which is likely responsible for their favorable homing.
| S-EPMC1847625 | biostudies-literature
Project description:Microarray data on TH cell subsets from WT C57BL/6 and Bhlhe40 KO mice We used microarrays to detail the global programme of gene expression in polarized TH cell lineages
2014-03-26 | GSE49166 | GEO
Project description:ILC2 contribute to tissue immunity by secreting large amounts of cytokines upon activation. However, their specific contribution to worm infection and epithelial remodeling remains incompletely understood. We tested the impact of ILC2 on tissue immunity in the colon of mice infected with the nematode Nippostronylus brasiliensis. We performed scRNA sequencing of colon epithelial cells from mice specifically lacking ILC2 (Nmur1-Cre Id2 fl/fl). Transcripts typically associated with type 2 immunity were reduced in ILC2-deficient mice, indicating a non-redundant role of ILC2 for type 2 tissue immunity in worm protection that cannot be compensated by other cell types. These findings highlight the importance of ILC2 for nematode control and type 2 tissue immunity.
2022-10-28 | GSE213424 | GEO
Project description:ILC2 contribute to immune homeostasis, protective immunity and tissue repair. However, an understanding of the microenvironmental factors and transcriptional circuits that support development of these innate lymphocytes within lymphoid organs, alongside their adaptive T and B cell relatives, is only starting to emerge. Here we demonstrate that functional ILC2 arise in the embryonic thymus, from shared T cell precursors, and precede the emergence of CD4+CD8+ (double-positive) T cells. Strikingly, RORa expression repressed T cell development, whilst promoting ILC2 in the thymus. Thymic ILC2 go on to contribute to the innate type-2 response at mucosal tissues with preferential colonisation of the intestinal lamina propria. From RNAseq, ATACseq and ChIPseq data we propose a revised transcriptional circuit to explain the enigmatic co-development of T cells, ILC2 and NK cells from common progenitors in the thymus. When Notch signalling is present, Bcl11b dampens Nfil3/Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORa overrides the Nfil3/Id2 repression, allowing Id2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORa expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.
2020-11-03 | GSE146743 | GEO