Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

47 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function - Innate lymphoid cells

ABSTRACT: Innate lymphoid cells (ILC) in the small intestine govern immune homeostasis and protect the host against gut pathogens. While distinct cell-intrinsic signals have been identified that determine ILC development and differentiation, it has remained unclear which cell population regulates ILC sustenance. Using unbiased single cell RNA transcriptomic analysis of intestinal fibroblasts, we have identified a specialized Ccl19-expressing fibroblastic reticular cell (FRC) population that underpins solitary intestinal lymphoid tissue (SILT) structures including cryptopatches and isolated lymphoid follicles. Conditional ablation of lymphotoxin-β receptor (LTβR) signalling in SILT FRC impeded the maturation of isolated lymphoid follicles and blocked ILC maintenance through the downregulation of IL-7, consequently resulting in the elevated susceptibility to bacterial infection. Moreover, specific Ltbr ablation in FRC during adulthood revealed that constant LTβR-dependent FRC-ILC interaction is required to maintain SILT structures and ILC populations. Taken together, our study unveils a critical intestinal FRC niche that secures protective gut immunity.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Mechthild Lütge

PROVIDER: E-MTAB-10645 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function - Intestinal fibroblasts

Project description:Innate lymphoid cells (ILC) in the small intestine govern immune homeostasis and protect the host against gut pathogens. While distinct cell-intrinsic signals have been identified that determine ILC development and differentiation, it has remained unclear which cell population regulates ILC sustenance. Using unbiased single cell RNA transcriptomic analysis of intestinal fibroblasts, we have identified a specialized Ccl19-expressing fibroblastic reticular cell (FRC) population that underpins solitary intestinal lymphoid tissue (SILT) structures including cryptopatches and isolated lymphoid follicles. Conditional ablation of lymphotoxin-β receptor (LTβR) signalling in SILT FRC impeded the maturation of isolated lymphoid follicles and blocked ILC maintenance through the downregulation of IL-7, consequently resulting in the elevated susceptibility to bacterial infection. Moreover, specific Ltbr ablation in FRC during adulthood revealed that constant LTβR-dependent FRC-ILC interaction is required to maintain SILT structures and ILC populations. Taken together, our study unveils a critical intestinal FRC niche that secures protective gut immunity.

2022-02-12 | E-MTAB-10638 | biostudies-arrayexpress

Innate lymphoid cell development requires TOX-dependent generation of a common ILC progenitor

Project description:Subtypes of innate lymphoid cells (ILC), defined by effector function and transcription factor expression, have recently been identified. In the adult, ILC derive from common lymphoid progenitors in bone marrow, although transcriptional regulation of the developmental pathways involved remains poorly defined. TOX is required for development of lymphoid tissue inducer cells, a type of ILC3 required for lymph node organogenesis, and NK cells, a type of ILC1. We show here that production of multiple ILC lineages requires TOX, as a result of TOX-dependent development of common ILC progenitors. Comparative transcriptome analysis demonstrated failure to induce various aspects of the ILC gene program in the absence of TOX, implicating this nuclear factor as a key early determinant of ILC lineage specification. TOX KO vs. wild tyype

2015-04-27 | E-GEOD-65850 | biostudies-arrayexpress

Single-cell deciphering of human fetal innate lymphoid cell development

Project description:The functions of innate lymphoid cells (ILCs) in immune system are increasingly appreciated, whereas the early development of ILCs in human remains elusive. In this study, we sorted humanhematopoietic stem progenitor cells, lymphoid progenitors, presumed ILC progenitor/precursors and mature ILCs in the fetal hematopoietic, lymphoid and non-lymphoid tissues, from 8 to 12 PCW,for single-cell RNA-sequencing, followed by computational analysis and functional validation. We delineated the early phase of ILC development, from hematopoietic stem progenitor cells to multipotent lymphoid progenitors and to ILC progenitors, which mainly occurred in fetal liver and intestine. We further unveiled interleukin-3 receptor alpha (IL-3RA) as the surface marker for the lymphoid progenitors with T cell, B cell and ILC potentials. Notably, we determined the heterogeneity and tissue distribution of each ILC subpopulation, revealing the shared proliferating characteristics of the precursors of each ILC subtype. Additionally, a novel unconventional ILC2 subpopulation (CRTH2-CCR9+ ILC2) was identified in fetal thymus. Taken together, our study illuminates the precise cellular and molecular features underlying the stepwise formation of human fetal ILC hierarchy with remarkable spatiotemporal heterogeneity.

2021-08-09 | GSE163587 | GEO

Development and differentiation of early innate lymphoid progenitors

Project description:Early innate lymphoid progenitors (EILP) have recently been identified in the mouse adult bone marrow as a multipotential progenitor population committed to ILC lineages, but their relationship with other described ILC progenitors is still unclear. In this study, we examine the progenitor-successor relationships between EILP, IL-7R+ common lymphoid progenitors (ALP), and ILC precursors (ILCp). Bioinformatic, phenotypical, functional, and genetic approaches collectively establish EILP as an intermediate progenitor between ALP and ILCp. Our work additionally provides new candidate regulators of ILC development and clearly defines the stage of requirement of transcription factors key for early ILC development.

2017-11-15 | GSE81530 | GEO

The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor

Project description:Innate lymphoid cells (ILCs) are recently identified lymphocytes that limit infection and promote tissue repair at mucosal surfaces. However, the pathways underlying ILC development remain unclear. Here we show that the transcription factor NFIL3 directs the development of a committed bone marrow precursor that differentiates into all known ILC lineages. NFIL3 was required in the common lymphoid progenitor (CLP), and was essential for the differentiation of CLP, a bone marrow cell population that gives rise to all known ILC lineages. Clonal differentiation studies revealed that CXCR6+ cells within the CLP population differentiate into all ILC lineages but not T- and B-cells. We further show that NFIL3 governs ILC development by directly regulating expression of the transcription factor TOX. These findings establish that NFIL3 directs the differentiation of a committed ILC precursor that gives rise to all ILC lineages and provide insight into the defining role of NFIL3 in ILC development. This experiment is to compare gene expression profiles between wild-type and Nfil3-/- common lymphoid progenitor (CLP) cells to identify genes regulated by NFIL3. There are 6 samples in this experiment, including 3 biological replicates for wild-type CLPs and 3 biological replicates for Nfil3-/- CLPs. All mice used are on the C57BL/6 background.

2014-10-16 | E-GEOD-62337 | biostudies-arrayexpress

RORÎ³t+ Innate lymphoid cells transcriptomes after aNKp44 and cytokine stimulation

Project description:RORÎ³t+ innate lymphoid cells (ILC) are crucial players of innate immune responses and represent a major source of IL-22, which has an important role in mucosal homeostasis. The signals required by RORÎ³t+ ILC to express IL-22 and other cytokines, including TNF, have only partially been elucidated. Here we show that RORÎ³t+ ILC can directly sense the environment by the engagement of the activating receptor NKp44. NKp44 triggering in RORÎ³t+ ILC selectively activates a coordinated pro-inflammatory program, including TNF, while cytokine stimulation induces preferentially IL-22 expression. However, combined engagement of NKp44 and cytokine receptors results in a strong synergistic effect. These data support the concept that NKp44+ RORÎ³t+ ILC can be activated without cytokines and are able to switch between IL-22 or TNF production, depending on the triggering stimulus. Transcriptome analysis of CD56+CD127hi tonsil ILC, Ex vivo and after stimulation with aNKp44, IL-1/IL-7/IL-23 or aNKp44/IL-1/IL-7/IL-23 for 3.5h. RNA was extracted and pooled from 2 donors each, Amplified and labeled according to manufacturerÂ´s instructions (GeneChipU133plus2Â® , Affymetrix). The analysis was performed in triplicates.

2013-10-30 | E-GEOD-43409 | biostudies-arrayexpress

Innate lymphoid cell development requires TOX-dependent generation of a common ILC progenitor

2015-04-27 | GSE65850 | GEO

Single cell analysis defines the divergence between the innate lymphoid cell and lymphoid tissue inducer lineages

Project description:The precise lineage relationships between innate lymphoid cells (ILC) and the lymphoid tissue inducer (LTi) are poorly understood. Using single-cell multiplex transcriptional analysis of 100 lymphoid genes and single-cell cultures of fetal liver precursor cells, we identified the common proximal precursor to these lineages and showed that its bifurcation was precisely marked by the differential induction of the transcription factors PLZF and TCF1. Acquisition of individual ILC1/2/3-specific effector programs was initiated later, at the common ILC precursor (ILCP) stage, by transient expression of mixed ILC1/2/3 transcriptional patterns whereas, in contrast, LTi development did not go through multilineage priming. These findings provide novel insights into divergent mechanisms of ILC and LTi lineage differentiation and establish a high-resolution map of their development.

2015-12-30 | GSE76407 | GEO

PD-1 regulates KLRG1+ group 2 innate lymphoid cells

Project description:Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens, allergens, tissue remodeling and metabolic homeostasis in response to cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated but co-receptor mediated negative regulatory axis is yet to be defined. We demonstrate that PD-1 is an important negative regulator of KLRG1+ILC-2 function in both mice and humans. Increase in KLRG1+ ILC-2 cells numbers were attributed to an intrinsic defect in PD-1 signaling, which resulted in enhanced STAT5 activation. During Nippostrongylus brasiliensis infection, a significant expansion of KLRG1+ ILC-2 subsets occurred in pdcd1-/- mice and on adoptive transfer, pdcd1-/- KLRG1+ ILC-2s significantly reduced worm burden. Furthermore, blocking antibody to PD-1 increased KLRG1+ ILC-2 cell number and reduced disease burden. Therefore PD-1 is an important negative regulator and is vital for maintaining the number and hence function of KLRG1+ ILC-2s.

2017-05-04 | GSE94609 | GEO