Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profile at single cell level of cells from the lungs of Mock and MuHV-4 infected mice.

ABSTRACT: The immunology of asthma is complex and involves the loss of immunoregulatory pathways with the adoption of a Western lifestyle inducing changes in the diversity and the time exposure to microorganisms. Gammaherpesviruses (γHVs) are among the most prevalent human viruses. Establishing early life infection, they profoundly imprint the immune system of their hosts. Using Murid herpesvirus 4 (MuHV-4), a mouse model of human γHV infections, we showed that both lung resident and bone marrow-derived group 2 innate lymphoid cells (ILC2s) displayed lasting reduced capacity to expand and to produce type 2 cytokines, in response to house dust mites, in an IFN-γ depend manner. Importantly, we uncovered that pulmonary ILC2s represent essential niche cells that imprint alveolar macrophage tissue-specific identity upon monocyte replenishment in infection settings. In particular, we showed that MuHV-4 infection disrupts the normal ILC2-epithelial cells circuit that imprints monocytes-derived AMs for type 2 functions without affecting their differentiation. These results reveal that persistent γHV infection shapes the alveolar landscape much beyond the initial acute infection through long-term effect on ILC2 niche cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE218247 | GEO | 2023/01/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression profile at single cell level of cells from the lungs of Mock and MuHV-4 infected mice after HDM challenge.

Project description:The immunology of asthma is complex and involves the loss of immunoregulatory pathways with the adoption of a Western lifestyle inducing changes in the diversity and the time exposure to microorganisms. Gammaherpesviruses (γHVs) are among the most prevalent human viruses. Establishing early life infection, they profoundly imprint the immune system of their hosts. Using Murid herpesvirus 4 (MuHV-4), a mouse model of human γHV infections, we showed that both lung resident and bone marrow-derived group 2 innate lymphoid cells (ILC2s) displayed lasting reduced capacity to expand and to produce type 2 cytokines, in response to house dust mites, in an IFN-γ depend manner. Importantly, we uncovered that pulmonary ILC2s represent essential niche cells that imprint alveolar macrophage tissue-specific identity upon monocyte replenishment in infection settings. In particular, we showed that MuHV-4 infection disrupts the normal ILC2-epithelial cells circuit that imprints monocytes-derived AMs for type 2 functions without affecting their differentiation. These results reveal that persistent γHV infection shapes the alveolar landscape much beyond the initial acute infection through long-term effect on ILC2 niche cells.

2023-01-05 | GSE218246 | GEO

Comparison of transcriptomic profiles of macrophages cultures without ILC2, in presence of ILC2 from uninfected mice, and in presence of ILC2 from MuHV-4 infected mice.

2023-01-05 | GSE218245 | GEO

Gene expression profile at single cell level of monocytes (MOs) and T cells from the lungs and from broncho-alveolar lavage fluids (BALF) from Mock and MuHV-4 infected WT and CCR2 KO mice.

Project description:Gammaherpesviruses (γHVs) have co-evolved with their hosts over millions of years, leading to remarkably high infection prevalence and establishment of symbiotic relationship. Therefore, the lifelong persistence of γHVs appear to broadly shape host immunity. Here, we show that pulmonary infection with Murid herpesvirus 4 (MuHV-4), a mouse γHV, drives the recruitment in the airways of Ly6Chi monocytes (MOs) that control the host immune response. Indeed, the absence of those MOs elicits a severe virus-induced immunopathology associated with the systemic release of inflammatory mediators. Mechanistically, MuHV-4 imprinted MOs recruit CD4 T cells in the airways and trigger immunosuppressive signalling pathways through the PDL1/PD-1 axis, thereby dampening the deleterious activation of cytotoxic CD4 T cells. These results uncover a role for Ly6Chi MOs in the modulation of CD4 T cell functions, and reveal key pathways that could be targeted to interfere with the detrimental immunopathological cascade during respiratory viral infections.

2022-06-14 | GSE205923 | GEO

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

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

Androgens protect murine ILC2 cells from functional suppression during influenza virus infection

Project description:Lung-resident group 2 innate lymphoid cells (ILC2s) produce type 2 cytokines and facilitate tissue repair in response to alarmins such as IL-33 released during respiratory virus infection, but they also may be functionally suppressed by type 1 cytokines. Compared to females, males harbor significantly fewer lung ILC2s, which express notably high levels of androgen receptor (AR) compared to other lymphocytes. Here we tested the hypothesis that females and males show differential ILC2 responses upon influenza virus (IAV) infection of mice. Over the course of sublethal infection, lungs of female mice contained greater numbers of ILC2s and ILC1s compared to males. However, the female ILC2s were preferentially suppressed at the peak of infection, with a dampened type 2 program manifest as attenuated proliferation, decreased propensity to produce IL-5 and amphiregulin, and reduced expression of GATA3 and IL-33R. Naïve female ILC2s showed higher expression of IFNGR and higher phospho-STAT1 levels following stimulation by IFN, and lymphocyte-restricted STAT1 deficiency reversed suppression of female ILC2s during infection. ILC2s in naive male mice with lymphocyte-restricted AR deficiency displayed levels of IFNGR comparable to female mice, suggesting AR activity underlies sex differences in intrinsic IFNGR expression. Early life orchiectomy or lymphocyte-restricted loss of AR revealed that endogenous androgens decreased ILC2 numbers but protected males from suppression of ILC2s in IAV infection. In sum, intrinsic AR activity preserves canonical ILC2 function in males during IAV infection, which may contribute to the sex differences in morbidity secondary to IAV observed in mice and humans.

2024-12-13 | GSE190941 | GEO

Transcriptome of Chat positive and negative ILC2s

Project description:Group 2 innate lymphoid cells (ILC2s) reside in multiple tissues including lymphoid organs and barrier surfaces, and secrete type 2 cytokines including interleukin (IL)-5, IL-9 and IL-13. These cells participate in multiple physiological processes including allergic inflammation, tissue repair, metabolic homeostasis and host defense against helminth infections. Recent studies indicate that neuropeptides can play an important role in regulating ILC2 responses, however, the mechanisms that underlie these processes in vivo remain incompletely defined. Here, we identify that activated ILC2s upregulate choline acetyltransferase (ChAT)—the enzyme responsible for the biosynthesis of acetylcholine (ACh)—following infection with the helminth parasite Nippostrongylus brasiliensis or treatment with alarmins or cytokines including IL-25, IL-33 and thymic stromal lymphopoietin (TSLP). ILC2s also express acetylcholine receptors (AChRs), and ACh administration promotes ILC2 cytokine production and elicits expulsion of helminth infection. In accordance with this, ChAT deficiency in ILC2s leads to defective ILC2 responses and impaired immunity against helminth infection. Together, these results reveal a previously unrecognized role of the ChAT-ACh pathway in promoting type 2 innate immunity to helminth infection.

2021-03-05 | GSE164705 | GEO

Chromatin accessibility landscapes of WT (GFP-) and BATF KO (GFP+) ILC3s sorted from lung mature ILC2s

Project description:Activated type 2 innate lymphoid cells (ILC2s) accumulate and promote inflammatory resolution and tissue repair in host defense against acute respiratory viral infections. However, the heterogeneity of ILC2s in the lung and the mechanisms by which ILC2 cells contribute to tissue repair remain elusive. Using single-cell RNA-sequencing (scRNA-seq), we identified a transcriptionally distinct ILC2 subset that showed enrichment for wound healing signature genes and the transcription factor BATF. Notably, BATF promoted the proliferation and function of ILC2s and restricted their plasticity during infection with influenza virus. In the absence of BATF, ILC2s lost their immune protective properties and obtained pathogenic ILC3-like function, which led to persist neutrophil infiltration, tissue damage and lethality. Mechanistically, BATF directly bound the cis-regulatory elements of wound healing genes, maintained their chromatin accessibility and promoted their expression. Lastly, BATF played an important role in an IL-33-ST2 feed-forward loop that supports ILC2 cell identity and function. Collectively, our findings shed light on a BATF-dependent ILC2 program, thereby providing a potential therapeutic target for terminating detrimental inflammation during acute viral infection.

2022-01-14 | GSE188275 | GEO

Retinoic acid drives intestine-specific adaptation of effector ILC2s originating from distant sites [scRNA-Seq]

Project description:Adaptation of immune cells to tissue-specific microenvironments is a crucial process in homeostasis and inflammation. Here, we show that murine effector type 2 innate lymphoid cells (ILC2s) from various organs are equally effective in repopulating ILC2 niches in other anatomical locations where they adapt tissue-specific phenotypes of target organs. Single-cell transcriptomics of ILC2 populations revealed upregulation of retinoic acid (RA) signaling in ILC2s during adaptation to the small intestinal microenvironment, and RA signaling mediated reprogramming of kidney effector ILC2s towards the small intestinal phenotype in vitro and in vivo. Inhibition of intestinal ILC2 adaptation by blocking RA signaling impaired worm expulsion during Strongyloides ratti infection, indicating functional importance of ILC2 tissue imprinting. In conclusion, this study highlights that effector ILC2s retain the ability to adapt to changing tissue-specific microenvironments, enabling them to exert tissue-specific functions, such as promoting control of intestinal helminth infections.

2023-09-15 | GSE242569 | GEO

Retinoic acid drives intestine-specific adaptation of effector ILC2s originating from distant sites [bulk RNA-Seq]

2023-09-15 | GSE242562 | GEO