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Homeostatic mature dendritic cells instruct fibroblast specialization via Notch2 to establish T cell niches

ABSTRACT: Secondary lymphoid organs are structurally organized by fibroblastic reticular cells (FRCs), which coordinate immune cell positioning and support adaptive immune responses. However, the mechanisms underlying the differentiation of FRCs into distinct functional subsets remain poorly understood. To investigate the role of Notch2 signaling in this process, we performed single-cell RNA sequencing (10x Genomics) on lymph node immune cells from mice lacking Notch2 expression specifically in FRCs. Our dataset reveals how Notch2 signaling shapes FRC subset differentiation and modulates the composition of neighboring immune cell populations.

ORGANISM(S): Mus musculus

PROVIDER: GSE294698 | GEO | 2026/04/22

REPOSITORIES: GEO

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Homeostatic mature dendritic cells instruct fibroblast specialization via Notch2 to establish T cell niches

Project description:Secondary lymphoid organs are structurally organized by fibroblastic reticular cells (FRCs), which support immune cell positioning and adaptive immune responses. However, the mechanisms driving the differentiation of FRCs into distinct functional subsets remain unclear. To investigate the role of Notch2 signaling in this process, we performed single-cell RNA sequencing (10x Genomics) on lymph node FRCs lacking Notch2 expression. Our dataset highlights how this pathway contributes to FRC differentiation.

2026-04-22 | GSE294697 | GEO

Homeostatic mature dendritic cells instruct fibroblast specialization via Notch2 to establish T cell niches

Project description:Secondary lymphoid organs are organized by fibroblastic reticular cells (FRCs), which direct immune cell positioning and support adaptive immunity. However, the mechanisms driving FRC subset differentiation remain unclear. To uncover signaling pathways involved in this process, we performed ATAC-seq on lymph node FRCs lacking Notch2. Our data reveal chromatin remodeling changes in the absence of Notch signaling.

2026-04-22 | GSE294695 | GEO

Transcriptomic profiling of immune and stromal cells from the non small cell lung cancer (NSCLC) environment

Project description:T lymphocytes can efficiently counteract the growth of tumors within the tumor microenvironment. Specialized immune-interacting fibroblasts, termed fibroblastic reticular cells (FRC) are responsible for the formation of specialized niches promoting immune cell activation in secondary lymphoid organs and originate from embryonic progenitors. FRCs have also been identified in tertiary lymphoid structures (TLS) in tumor tissues. However, the identity and differentiation of TLS-associated FRC subsets that promote intra-tumoral T cell activity have remained unexplored. Here, we employed single cell RNA-sequencing of fibroblasts and immune cells, sampled from subpleural margin, central margin and unaffected lung tissue in non small cell lung cancer (NSCLC), demonstrating the formation of specific tumor T cell environments (TTEs) underpinned by CCL19-expressing FRCs. We detected tumor-specific FRC subsets namely CCL19-expressing TRCs and perivascular reticular cells (PRCs) interacting with intratumoral T cells, and thus regulating FRC differentiation and T cell activation. Our results highlight a remarkable functionality of FRCs to efficiently determine protective antitumoral T cell responses in NSCLC.

2024-11-19 | E-MTAB-13710 | biostudies-arrayexpress

Fibroblastic reticular cells serve as primary immune checkpoint in visceral adipose tissues and secure peritoneal immunity

Project description:Immune protection of the body cavities depends on the swift activation of innate and adaptive immune responses in non-classical secondary lymphoid organs known as fat-associated lymphoid clusters (FALCs). While it is well-established that fibroblastic reticular cells (FRCs) are an integral component of the immune-stimulating infrastructure of lymph nodes and other classical secondary lymphoid organs, it has remained elusive whether and how FRCs in FALCs contribute to peritoneal immunity. Using FRC-specific gene targeting, we found that FALCs are underpinned by an elaborated FRC network and that initiation of peritoneal immunity was governed through FRC activation via MyD88-dependent innate immunological sensing. FRC-specific ablation of Myd88 expression blocked recruitment of inflammatory monocytes into FALCs and subsequent CD4+ T cell-dependent B-cell activation. Moreover, containment of Salmonella infection was compromised in conditionally Myd88-deficient mice indicating that FRCs in FALCs function as initial checkpoint in the orchestration of protective immune responses in the peritoneal cavity.

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Single-cell RNA sequencing reveals tissue-associated fibroblastic reticular cell heterogeneity in human secondary lymphoid organs

Project description:Fibroblastic reticular cells (FRCs) actively support secondary lymphoid organ (SLO) architecture. They regulate innate and adaptive immunity by compartmentalizing immune cells in specialized niches, and tightly interacting with them. The phenotypic and functional diversity of FRCs in human SLOs remains largely uncharacterized. We performed a comprehensive profiling of FRCs by single-cell RNA sequencing on human tonsils and lymph nodes. We provide the first complete description of the tonsillar CD45-negative compartment. We identified and validated in tonsil, a population of follicular dendritic cells restricted to the mantle zone and discovered two CCL21-negative FRC subsets intermingling with T-cell zone reticular cells in the extrafollicular space. We also identified podoplanin-positive epithelial cells as a potential plasma cell (PC) niche. We found two levels of FRC-associated diversity: i) tissue-specific subsets; ii) shared subsets with tissue-specific gene signatures. These findings shed new light on the role of FRCs in supporting SLO-specific immune responses.

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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

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

2022-02-12 | E-MTAB-10645 | biostudies-arrayexpress

Single cell RNAseq of immune and stromal cells in murine lung cancer

Project description:Immune responses against tumor cells depend on T lymphocyte attraction and activity within the tumor microenvironment. Specialized immune-interacting fibroblasts, commonly referred to as fibroblastic reticular cells (FRC), form specialized niches in secondary lymphoid organs, originate from embryonic progenitors and foster T cell activation. FRCs have also been detected in tertiary lymphoid structures (TLS) in tumors, differentiating from cancer associated fibroblasts. However, the identity and differentiation of niche-forming cells that foster intra-tumoral T cell activity have remained elusive. Here, we employed single cell RNA-sequencing of EYFP+ fibroblasts and GP33/34-Tetramer+CD8+ T cells from experimental murine lung cancer and cell fate-mapping analysis, which revealed the ability of FRC subsets in lung tumors to differentiate from progenitors situated in mural and adventitial sites. Ablation of FRC progenitors in Tumor T cell environments (TTEs) of murine lungs led to reduced anti-tumor T cell activity and loss of tumor control during experimental coronavirus vector-based immunotherapy. Collectively, our study defines lung cancer-associated FRC niches and key processes involved in stromal-T cell interaction that could pave the way for improved cancer immunotherapy.

2024-11-19 | E-MTAB-13708 | biostudies-arrayexpress

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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

Activation of TLR9 signaling suppresses the immuno modulating functions of CD55lo fibroblastic reticular cells during bacterial peritonitis

Project description:Fibroblastic reticular cells (FRCs) are heterogeneous. We use single cell RNA sequencing to identify subsets of FRCs in fat-associated lymphoid clusters (FALC) in the mesenteric adipose tissue

2024-04-18 | GSE250571 | GEO

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