Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neonatally imprinted mesenteric lymph node stromal cell subsets induce tolerogenic dendritic cells [endogenous FSCs]

ABSTRACT: Gut-draining mesenteric lymph nodes (mLNs) play a key role in peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment for efficient de novo induction of Foxp3+ regulatory T cells (Tregs). We recently identified mLN stromal cells as critical cellular players in this process and demonstrated that their tolerogenic properties are imprinted by microbiota. Here, we show that this imprinting process already takes place in the neonatal phase and renders the mLN stromal cell compartment resistant to inflammatory perturbations later in life. Utilizing LN transplantation, RNA-seq and single-cell RNA-seq allowed identification of stably imprinted expression signatures in mLN fibroblastic stromal cells. We dissected common stromal cell subsets across gut-draining mLNs and skin-draining LNs with location-specific immunomodulatory functions, such as subset-specific expression of Aldh1a2/3. Accordingly, mLN stromal cells shaped resident dendritic cells to attain high Treg-inducing capacity in a Bmp2-dependent manner. Thus, crosstalk between mLN stromal and resident dendritic cells provides a robust feedback mechanism for the maintenance of intestinal tolerance.

ORGANISM(S): Mus musculus

PROVIDER: GSE79435 | GEO | 2018/09/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Neonatally imprinted mesenteric lymph node stromal cell subsets induce tolerogenic dendritic cells [resDCs]

Project description:Gut-draining mesenteric lymph nodes (mLNs) play a key role in peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment for efficient de novo induction of Foxp3+ regulatory T cells (Tregs). We recently identified mLN stromal cells as critical cellular players in this process and demonstrated that their tolerogenic properties are imprinted by microbiota. Here, we show that this imprinting process already takes place in the neonatal phase and renders the mLN stromal cell compartment resistant to inflammatory perturbations later in life. Utilizing LN transplantation, RNA-seq and single-cell RNA-seq allowed identification of stably imprinted expression signatures in mLN fibroblastic stromal cells. We dissected common stromal cell subsets across gut-draining mLNs and skin-draining LNs with location-specific immunomodulatory functions, such as subset-specific expression of Aldh1a2/3. Accordingly, mLN stromal cells shaped resident dendritic cells to attain high Treg-inducing capacity in a Bmp2-dependent manner. Thus, crosstalk between mLN stromal and resident dendritic cells provides a robust feedback mechanism for the maintenance of intestinal tolerance.

2018-09-25 | GSE106882 | GEO

Neonatally imprinted mesenteric lymph node stromal cell subsets induce tolerogenic dendritic cells [migDC]

2018-09-25 | GSE115950 | GEO

Neonatally imprinted mesenteric lymph node stromal cell subsets induce tolerogenic dendritic cells [Tx FSC]

2018-09-25 | GSE106636 | GEO

Neonatal imprinting of mesenteric lymph node stroma modulates tolerogenic properties of dendritic cells [scRNA-seq]

2018-09-25 | GSE106489 | GEO

Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3+ regulatory T cells.

Project description:Intestinal regulatory T cells (Tregs) are fundamental in peripheral tolerance toward commensals and food-borne antigens. Accordingly, gut-draining mesenteric lymph nodes (mLNs) represent a site of efficient peripheral de novo Treg induction when compared to skin-draining peripheral LNs (pLNs), and we had recently shown that LN stromal cells substantially contribute to this process. Here, we aimed to unravel the underlying molecular mechanisms and generated immortalized fibroblastic reticular cell lines (iFRCs) from mLNs and pLNs, allowing unlimited investigation of this rare stromal cell subset. In line with our previous findings, mLN-iFRCs showed a higher Treg-inducing capacity when compared to pLN-iFRCs. RNA-seq analysis focusing on secreted molecules revealed a more tolerogenic phenotype of mLN- as compared to pLN-iFRCs. Remarkably, mLN-iFRCs produced substantial numbers of microvesicles (MVs) that carried elevated levels of TGF-β when compared to pLN-iFRC-derived MVs, and these novel players of intercellular communication were shown to be responsible for the tolerogenic properties of mLN-iFRCs. Thus, stromal cells originating from mLNs contribute to peripheral tolerance by fostering de novo Treg induction using TGF-β-carrying MVs. This finding provides novel insights into the subcellular/molecular mechanisms of de novo Treg induction and might serve as promising tool for future therapeutic applications to treat inflammatory disorders.

2017-08-30 | GSE93670 | GEO

Vitamin A treatment rescues neonatal infection-induced durably impaired lymph node function (scRNA-Seq)

Project description:Gut-draining mesenteric and celiac lymph nodes (mLNs and celLNs) critically contribute to peripheral tolerance towards food and microbial antigens by efficiently supporting the de novo induction of regulatory T cells (Tregs). These tolerogenic properties of mLNs and celLNs are stably imprinted within stromal cells (SCs) by microbial signals and vitamin A (VA), respectively. In the present study, we demonstrated that a transient neonatal gastrointestinal infection long-lastingly affects the functionality of celLN by permanently abrogating the efficient Treg-inducing capacity of celLN SCs. The neonatal infections durably shifted the heterogeneity of celLN SCs with permanently altered expression of genes involved in chemotaxis and inflammatory responses, resulting in a lastingly skewed dendritic cell (DC) composition. Mechanistically, transiently reduced VA levels caused the long-lastingly impaired celLN function, which could be rescued by an early-life VA supplementation. Together, our data highlight the therapeutic potential of VA treatment post gastrointestinal infections in infants.

2023-12-31 | GSE183390 | GEO

Postnatal expansion of the lymph node stromal cell pool towards reticular and CD34+ stromal cell subsets [BRB-seq]

Project description:Gut-draining mesenteric lymph nodes (mLNs) provide the framework to shape intestinal adaptive immune responses. We previously delineated transcriptional signatures in LN stromal cells (SC), pointing to tissue-specific variability in SC composition and immunomodulatory function. Here, using scRNA-seq we dissected the developmental trajectory of SCs within mLNs derived from postnatal to aged mice, and identified two putative progenitors, namely CD34+ SC and fibroblastic reticular stromal cell (FRC) progenitors, which both feed the rapid LN expansion postnatally. We further unraveled the tissue-specific chromatin accessibility and DNA methylation landscape of non-endothelial SCs, and identified a microbiota-independent core epigenomic signature, showcasing differences between SCs from mLN and skin-draining peripheral LN. Irf3 was inferred from the epigenomic landscape of SCs, being dynamically expressed along the differentiation trajectories of FRCs. Lentiviral overexpression of Irf3 in a mesenchymal stem cell line established a Cxcl9+ FRC molecular phenotype. The relevance of Irf3 for SC biology was further underscored by the diminished proportion of Ccl19+ and Cxcl9+ FRCs in LNs from Irf3-/- mice. Together, our data constitute a comprehensive transcriptional and epigenomic map of LNSC development in early life and dissect location-specific, microbiota-independent properties of non-endothelial SCs.

2022-10-07 | GSE171901 | GEO

Postnatal expansion of the lymph node stromal cell pool towards reticular and CD34+ stromal cell subsets [RNA-seq]

2022-10-07 | GSE171903 | GEO

Postnatal expansion of the lymph node stromal cell pool towards reticular and CD34+ stromal cell subsets [scRNA-seq]

2022-10-07 | GSE172514 | GEO