Splenic fibroblastic reticular cells regulate dendritic cell maturation and T-DC interactions required for antiviral immunity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1148487 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30252608_1.fastq.gz | Fastqsanger.gz | |||
| SRR30252608_2.fastq.gz | Fastqsanger.gz | |||
| SRR30252609_1.fastq.gz | Fastqsanger.gz | |||
| SRR30252609_2.fastq.gz | Fastqsanger.gz | |||
| SRR30252610_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Stromal cells construct the architecture of the spleen and provide crucial signals that influence the homeostasis and migration of immune cells in the steady state. Fibroblastic Reticular Cells (FRCs) respond to infection via the regulation of many key structural and functional components. Yet, how spleen FRCs contribute to the induction and maintenance of antiviral T cell responses is still poorly defined. We found that ablation of splenic FRCs impacted the generation of virus-specific CD8 T cell during lymphocytic choriomeningitis virus (LCMV) infection in mice. Imaging revealed that during T cell priming in the presence of FRCs, CD8 T cells clustered in the T cell zone with type 1 conventional dendritic cells (cDC1) before moving to the marginal zone to interact with virus-infected cells. In the absence of FRCs, T cells instead clustered with virus-infected cells and cDC1s in the marginal zone, undergoing suboptimal priming due to reduced TCR signalling and unstable DC-T cell interactions. We found that FRCs regulated the early inflammatory wave required for optimal DC activation in vivo. The absence of FRCs thus resulted in diminished DC activation and impaired capacity to prime T cell responses. We further revealed that the presence of an intact FRC network was crucial for the generation of functional effector T cells. Importantly, these early cellular events orchestrated by FRCs also regulated the generation of protective memory T cells upon resolution of infection. Altogether, our study reveals important roles for FRCs for induction of antiviral T cell responses through support for DC maturation, effector CTL generation and the formation of protective memory T cells.
2024-08-16 | GSE274926 | GEO
Project description:Splenic white pulp (WP) structures are underpinned by fibroblastic stromal cells (FSCs) to facilitate splenic compartmentalization and execute efficient immune responses. Although distinct WP FSCs exhibit various molecular traits, the origin and the hierarchical differentiation of different cell subsets are not characterized. Here we showed, the organization of splenic WP and the differentiation of WP FSCs were governed by lymphotoxin beta receptor (LTβR) signaling pathway. Cell fate mapping analysis revealed that different WP fibroblastic stromal cells descend from a common perivascular LTβR-sensitive mesenchymal lymphoid organizer cells (mLTo) at prenatal stage. Moreover, embryonic mLTo cells required LTβR signaling to give rise to different WP stromal cell subsets, while the proliferation of these cells was devoid of LTβR signaling but followed the development of WP during ontogeny. Moreover, cell fate mapping from different time point indicated a consecutive commitment of mLTo cells initiated from the proximal region around the splenic artery. RNAseq and differentiation trajectory analysis of distinct FSCs showed that Ltbr-deficient cells and perivascular reticular cells (PRCs) from adult spleen exhibited a progenitor phenotype and revealed a closer hierarchical lineage with embryonic mLTo cells. Taken together, our results unveil that embryonic mLTo cells residing in the perivascular niches can give rise to different FSC populations in a LTβR-dependent manner during development.
2019-03-27 | E-MTAB-7703 | biostudies-arrayexpress
Project description:Splenic white pulp (WP) structures are underpinned by fibroblastic stromal cells (FSCs) to facilitate splenic compartmentalization and execute efficient immune responses. Although distinct WP FSCs exhibit various molecular traits, the origin and the hierarchical differentiation of different cell subsets are not characterized. Here we showed, the organization of splenic WP and the differentiation of WP FSCs were governed by lymphotoxin beta receptor (LTβR) signaling pathway. Cell fate mapping analysis revealed that different WP fibroblastic stromal cells descend from a common perivascular LTβR-sensitive mesenchymal lymphoid organizer cells (mLTo) at prenatal stage. Moreover, embryonic mLTo cells required LTβR signaling to give rise to different WP stromal cell subsets, while the proliferation of these cells was devoid of LTβR signaling but followed the development of WP during ontogeny. Moreover, cell fate mapping from different time point indicated a consecutive commitment of mLTo cells initiated from the proximal region around the splenic artery. RNAseq and differentiation trajectory analysis of distinct FSCs showed that Ltbr-deficient cells and perivascular reticular cells (PRCs) from adult spleen exhibited a progenitor phenotype and revealed a closer hierarchical lineage with embryonic mLTo cells. Taken together, our results unveil that embryonic mLTo cells residing in the perivascular niches can give rise to different FSC populations in a LTβR-dependent manner during development.
2019-03-27 | E-MTAB-7094 | biostudies-arrayexpress
Project description:Splenic white pulp (WP) structures are underpinned by fibroblastic stromal cells (FSCs) to facilitate splenic compartmentalization and execute efficient immune responses. Although distinct WP FSCs exhibit various molecular traits, the origin and the hierarchical differentiation of different cell subsets are not characterized. Here we showed, the organization of splenic WP and the differentiation of WP FSCs were governed by lymphotoxin beta receptor (LTβR) signaling pathway. Cell fate mapping analysis revealed that different WP fibroblastic stromal cells descend from a common perivascular LTβR-sensitive mesenchymal lymphoid organizer cells (mLTo) at prenatal stage. Moreover, embryonic mLTo cells required LTβR signaling to give rise to different WP stromal cell subsets, while the proliferation of these cells was devoid of LTβR signaling but followed the development of WP during ontogeny. Moreover, cell fate mapping from different time point indicated a consecutive commitment of mLTo cells initiated from the proximal region around the splenic artery. RNAseq and differentiation trajectory analysis of distinct FSCs showed that Ltbr-deficient cells and perivascular reticular cells (PRCs) from adult spleen exhibited a progenitor phenotype and revealed a closer hierarchical lineage with embryonic mLTo cells. Taken together, our results unveil that embryonic mLTo cells residing in the perivascular niches can give rise to different FSC populations in a LTβR-dependent manner during development.
2019-03-27 | E-MTAB-7097 | biostudies-arrayexpress
Project description:Fibroblastic reticular cells (FRCs) (CD45- Ter119-MADCAM1- CD21/35- CD31- PDPN-) from skin draining lymph nodes of Grem1-Cre-ERT2.cki; Rosa26-LSL-EYFP mice were sorted and subjected to bulk RNA-seq of Grem1 reporter + and Grem1 reporter - cells.
2021-04-10 | E-MTAB-10205 | biostudies-arrayexpress
Project description:Fibroblastic reticular cells (FRC) shape the organization of secondary lymphoid organs and actively promote the induction of immune responses by coordinating the interaction of innate and adaptive immune cells. However, the mechanisms underlying FRC functions during viral infections have remained largely unexplored. In the study, we combined FRC-specific genetic ablation of the type 1 IFN-alpha receptor (IFNAR) with high-dimensional transcriptomics analyses to elaborate the phenotypical alterations and functional consequences of impaired innate immunological sensing in FRC during lymph node-restricted viral infection
2020-09-01 | E-MTAB-8906 | biostudies-arrayexpress
Project description:Bulk RNA-seq of Fibroblastic Reticular Cells
| PRJEB43610 | ENA
Project description:Origin and differentiation trajectories of fibroblastic reticular cells in the splenic white pulp - bulk RNAseq
| PRJEB28026 | ENA
Project description:We report the transcriptome of subsets of mouse splenic mesenchymal reticular cells and lymph node reticular cells obtained from healthy Ccl19-cre x R26R-EYFP mice on a C57BL/6 background. We also examine splenic reticular cells from these mice infected with lymphocytic choriomeningitis virus (LCMV) strain Armstrong (acute infection) or strain Clone 13 (chronic infection). Subsets of CD45- CD31- Ter119- reticular cells were analyzed including PDPN+ T zone reticular cells (TRC) and MAdCAM-1+ marginal reticular cells (MRC) from spleen and lymph nodes. Additionally from the spleen we analyzed PDPN+ CD140a- cells, PDPN+ EYFP- cells, and EYFP+ red pulp reticular cells (RPRC) in healthy mice. We analyzed TRC, MRC, PDPN+ EYFP- cells, and EYFP+ RPRC from mice infected with LCMV Armstrong or LCMV Clone-13 on day 8 or on day 30 after infection. Our study represents the first detailed analysis of splenic reticular cell transcriptomes in healthy and LCMV-infected mice, with biologic replicates, generated by RNA-sequencing. We find substantial differential gene expression across subsets of splenic and lymph node reticular cells. We reveal significant changes in gene expression induced after virus infection that differ markedly with disease.
2022-01-09 | GSE171124 | GEO