Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bone marrow progenitors and IL-2 signaling contribute to the strain differences of kidney innate lymphoid cells

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE208404 | GEO | 2023/01/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcription factor Bcl11b controls identity and function of mature innate lymphoid cells type II

Project description:Type-2 innate lymphoid cells (ILC2s) promote anti-helminth responses and contribute to allergies. Though Bcl11b has been previously considered a T-lineage identity transcription factor (TF) that restrains the innate-cell genetic programs, we report here that Bcl11b is highly expressed in mature ILC2s and acts upstream of the key ILC2 TFs Gfi1, Gata-3, and of IL-33 receptor IL1rl1 (T1ST2). Additionally, Bcl11b-/- ILC2s de-repressed Rorγt, Ahr and IL-23 receptor, normally expressed in type-3 ILCs (ILC3s). Consequently, Bcl11b-/- ILC2s lost ILC2 functions and gained ILC3 functions, expanding in response to the protease allergen papain, however producing IL-17 and IL-22, and not IL-5 and IL-13, causing lung neutrophilia rather than eosinophilia, and diminished mucus production. Our results broaden Bcl11b's role from a T-cell only TF, and establishes that Bcl11b sustains mature ILC2 genetic and functional programs and lineage fidelity through positive regulation of essential ILC2 TFs and negative regulation of pivotal ILC3 TFs. RNA-seq analysis on sorted ILC2s from the mLNs of Bcl11bF/F Cre-ERT2 and wildtype mice at steady state following tamoxifen mediated deletion of Bcl11b

2015-07-28 | E-GEOD-67437 | biostudies-arrayexpress

Neuromedin U receptor-1 amplifies inflammatory lung innate lymphoid cells

Project description:Type 2 innate lymphoid cells (ILC2s) promote mucosal homeostasis, yet also contribute to pathologic type 2 inflammation in allergic asthma. Alarmin cytokines produced by damaged and stressed epithelial cells, such as IL-25, activate ILC2s, but it remains unclear if these cytokines are unique in switching homeostatic ILC2s into pro-inflammatory cells that drive tissue inflammation. To identify molecular cues that modulate ILC responses to alarmins, we collected single-cell RNA-seq profiles of lung-resident ILCs at steady state and after in vivo stimulation. Computational and functional analysis identified that ILC2s express the neuropeptide receptor Nmur1. Neuromedin U (NMU), the ligand of Nmur1, activates ILCs in vitro, and when co-administered with IL-25 in vivo, NMU dramatically amplifies allergic inflammation and induces ILC2 expansion. Finally, loss of NMU/Nmur1-signaling reduces ILC2 frequency and effector function following allergen challenge in vivo. Our results demonstrate that Nmur1 signaling modifies alarmin-mediated ILC2 responses to promote pro-inflammatory ILCs, and highlights the importance of neuro-immune crosstalk in allergic inflammatory responses at mucosal surfaces.

2017-09-17 | GSE102299 | GEO

Transcription factor Bcl11b controls identity and function of mature innate lymphoid cells type II

2015-07-28 | GSE67437 | GEO

Unconventional ST2- and CD127-negative lung ILC2 populations are induced by Alternaria

Project description:Background: Alternaria exposure is associated with severe asthma in humans. Alternaria exposure in mice potently activates group 2 innate lymphoid cells (ILC2s) via the IL-33/ST2 axis and causes ILC2s to robustly secrete type 2 cytokines. Objective: Our aim was to determine whether conventionally used ILC2 markers, ST2 (IL-33R) and CD127 (IL-7Ra), were sufficient to identify all Th2-cytokine producing ILCs after Alternaria exposure. Methods: Mice received intranasal Alternaria for three days prior to analysis. Lung ILCs were identified by flow cytometry as CD45+Lineage−Thy1.2+ lymphocyte-sized cells, divided into four subsets based on ST2 and CD127 expression, and stained for intracellular cytokines and transcription factors. Sort-purified ILC subpopulations were also analyzed by RNA sequencing and qPCR. Results: Alternaria exposure led to accumulation of all ILC populations regardless of ST2 or CD127 expression. Nearly half of the GATA-3+, IL-5+, and IL-13+ ILCs were “unconventional” as they were either single or double negative for ST2/CD127. Further, these populations upregulated CD25, KLRG1, and ICOS after Alternaria challenge. Some activated unconventional IL-5+ ILC2s also produced IFNγ and IL-17A. In addition to shared ILC2 transcripts (Gata3, Il5, Il13) in all populations, RNA-seq further identified novel transcripts enriched in each subset. Finally, transcripts from all populations that correlated best with IL-5 and IL-13 production included Tnfrsf18, Ffar2, and Pde4b. Conclusions: Unconventional ST2- and CD127-negative mouse lung ILC2 populations are induced by Alternaria. Thus, commonly used lung ILC2 identification methods based on ST2 and CD127 do not accurately account for the total ILC2 burden and may exclude nearly half of these cells.

2019-08-22 | GSE136156 | GEO

Human ILC2 cells stimulated with IL-25, IL-33, or TSLP

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

Expression data from naive, effector and memory-like ILC2s isolated from mouse lungs and those from effector and memory-like ILC2s isolated from mediastinal lymph node

Project description:Group 2 innate lymphoid cells (ILC2s) in the lung are stimulated by inhaled allergens. ILC2s do not directly recognize allergens but they are stimulated by cytokines including interleukin (IL)-33 released by damaged epithelium.Lung ILC2s, upon stimulation, produce T helper 2 cell-type cytokines inducing T cell independent allergic lung inflammation. We now report that lung ILC2s, upon activation by an allergen or IL-33, acquire the properties of memory cells. The activated ILC2s initially proliferate and secrete cytokines, followed by a contraction phase as they stop producing cytokines. Nevertheless, some persist long after the resolution of the inflammation and acquire intrinsic capacities to react to unrelated allergens more vigorously than naÃ¯ve ILC2s, thus mediating a severe allergic lung inflammation. Gene expression profiles of the previously activated ILC2s show a gene signature of memory T cells. These antigen non-specific memory ILC2s may explain why asthma patients are often sensitized to multiple allergens. ILC2s were isolated from mouse lungs from naive and IL-33 injected mice 4 days, 14 days and 4 months after the initial treatment. RNA was extracted from those ILC2 populations and analyzed for gene expression profiles. RNA was also extracted from ILC2s isolated from lung draining mediastinal lymph node (mLN) 4 days and 14 days after IL-33 treatment.

2016-06-30 | E-GEOD-81700 | biostudies-arrayexpress

Skin-resident innate lymphoid cells converge on a pathogenic effector state

Project description:Tissue-resident innate lymphoid cells (ILCs) help sustain barrier function and respond to local signals. ILCs are traditionally classified as ILC1, ILC2 or ILC3 on the basis of their expression of specific transcription factors and cytokines1. In the skin, disease-specific production of ILC3-associated cytokines interleukin (IL)-17 and IL-22 in response to IL-23 signalling contributes to dermal inflammation in psoriasis. However, it is not known whether this response is initiated by pre-committed ILCs or by cell-state transitions. Here we show that the induction of psoriasis in mice by IL-23 or imiquimod reconfigures a spectrum of skin ILCs, which converge on a pathogenic ILC3-like state. Tissue-resident ILCs were necessary and sufficient, in the absence of circulatory ILCs, to drive pathology. Single-cell RNA-sequencing (scRNA-seq) profiles of skin ILCs along a time course of psoriatic inflammation formed a dense transcriptional continuum—even at steady state—reflecting fluid ILC states, including a naive or quiescent-like state and an ILC2 effector state. Upon disease induction, the continuum shifted rapidly to span a mixed, ILC3-like subset also expressing cytokines characteristic of ILC2s, which we inferred as arising through multiple trajectories. We confirmed the transition potential of quiescent-like and ILC2 states using in vitro experiments, single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) and in vivo fate mapping. Our results highlight the range and flexibility of skin ILC responses, suggesting that immune activities primed in healthy tissues dynamically adapt to provocations and, left unchecked, drive pathological remodelling.

2020-12-14 | GSE149622 | GEO

Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid

Project description:We aimed to determine the characteristic of IL-10-producing ILCs induced from ILC2s by RA. We found that IL-10-producing ILCs has distinct characteristic compared to IL-10 negative ILCs.

2019-01-26 | GSE110278 | GEO

Group 3 innate lymphoid cells continuously require the transcription factor GATA3 after commitment

Project description:GATA3 is indispensable for the development of all IL-7RÎ±-expressing innate lymphoid cells (ILCs) and maintenance of type 1 ILCs (ILC1s) and type 2 ILCs (ILC2s). However, the importance of low GATA3 expression in type 3 ILCs (ILC3s) is still elusive. Here, we report that GATA3 regulates homeostasis of ILC3s by controlling IL-7RÎ± expression. In addition, GATA3 is critical for the development of NKp46+ ILC3 subset partially through regulating the balance between T-bet and RORÎ³t. Genome-wide analyses indicate that while GATA3 positively regulates CCR6+ and NKp46+ ILC3 subset-specific genes in respective lineages, it negatively regulates CCR6+ ILC3-specific genes in NKp46+ ILC3s. Furthermore, GATA3 regulates IL-22 production in both CCR6+ and NKp46+ ILC3s. Thus, low GATA3 expression is critical for the development and function of ILC3 subsets. To identify GATA3 regulated genes in total ILC3s with RNA-Seq; To identify unique genes expressed by CCR6+ ILC3 or NKp46+ ILC3 and GATA3 regulated genes within these two ILC3 subsets with RNA-Seq; To identify GATA3 direct binding sites in ILC3s, ILC2s and Th2 cells with ChIP-Seq.

2015-11-23 | E-GEOD-71198 | biostudies-arrayexpress

RNA-seq analysis of the Innate Lymphoid Cells type 2 (ILC2) or their precursors (ILC2p ) sorted from WT and Tgfbr2-/- mice

Project description:Purpose: The molecular pathways underlying the development of innate lymphoid cells (ILCs) are mostly unknown. Results: TGF-β signaling programs the development of ILC2s from their progenitors. Specifically, the deficiency of TGF-β receptor II in bone marrow progenitors results in inefficient development of ILC2s, but not ILC1s or ILC3s. We found that hundreds of genes were changed in Tgfbr2-/- ILC2s compared to WT ILC2s (FDR < 0.1 and Fold-Change >1.5). Some ILC2-associated genes including Gata3, Il1rl1 (ST2), Il-5, Atxn1 (Sca1), and Ccr4 were decreased in Tgfbr2-/- ILC2s, according to RNA-seq analysis Conclusions: TGF-β upregulates the expression of the IL-33 receptor gene Il1rl1 (encoding IL-1 receptor-like 1, also known as ST2) in ILC2p and common helper-like innate lymphoid progenitors (CHILP), at least partially through the MEK-dependent pathway. These findings identify a function of TGF-β in the development of ILC2s from their progenitors.

2019-11-09 | GSE140168 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data