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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE116633 | GEO | 2018/09/25

REPOSITORIES: GEO

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Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes.

Project description:Gut-draining mesenteric lymph nodes (mLNs) are important for inducing peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment for de novo generation of Foxp3+ regulatory T cells (Tregs). We previously identified microbiota-imprinted mLN stromal cells as a critical component in tolerance induction. 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. LN transplantation and single-cell RNA-seq uncover stably imprinted expression signatures in mLN fibroblastic stromal cells. Subsetting common stromal cells across gut-draining mLNs and skin-draining LNs further refine their location-specific immunomodulatory functions, such as subset-specific expression of Aldh1a2/3. Finally, we demonstrate that mLN stromal cells shape 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 regulatory mechanism for the maintenance of intestinal tolerance.

| S-EPMC6156403 | biostudies-literature

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

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 | GSE115950 | GEO

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

2018-09-25 | GSE106882 | GEO

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

2018-09-25 | GSE106636 | GEO

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

2018-09-25 | GSE79435 | GEO

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

Project description:Neonatally imprinted mesenteric lymph node stromal cell subsets induce tolerogenic dendritic cells

| PRJNA479754 | ENA

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

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

| PRJNA418310 | ENA

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

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

| PRJNA476578 | ENA

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

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

| PRJNA417486 | ENA

Postnatal expansion of mesenteric lymph node stromal cells towards reticular and CD34<sup>+</sup> stromal cell subsets.

Project description:Gut-draining mesenteric lymph nodes (LN) provide the framework to shape intestinal adaptive immune responses. Based on the transcriptional signatures established by our previous work, the composition and immunomodulatory function of LN stromal cells (SC) vary according to location. Here, we describe the single-cell composition and development of the SC compartment within mesenteric LNs derived from postnatal to aged mice. We identify CD34+ SC and fibroblastic reticular stromal cell (FRC) progenitors as putative progenitors, both supplying the typical rapid postnatal mesenteric LN expansion. We further establish the location-specific chromatin accessibility and DNA methylation landscape of non-endothelial SCs and identify a microbiota-independent core epigenomic signature, showing characteristic differences between SCs from mesenteric and skin-draining peripheral LNs. The epigenomic landscape of SCs points to dynamic expression of Irf3 along the differentiation trajectories of FRCs. Accordingly, a mesenchymal stem cell line acquires a Cxcl9+ FRC molecular phenotype upon lentiviral overexpression of Irf3, and the relevance of Irf3 for SC biology is further underscored by the diminished proportion of Ccl19+ and Cxcl9+ FRCs in LNs of Irf3-/- mice. Together, our data constitute a comprehensive transcriptional and epigenomic map of mesenteric LNSC development in early life and dissect location-specific, microbiota-independent properties of non-endothelial SCs.

| S-EPMC9700677 | biostudies-literature

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