Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Adult mouse skin dendritic cells

ABSTRACT: Early life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here we show that this process is controlled by microbial interaction with a specialized subset of antigen presenting cells. More particularly, we identify CD301b+ type 2 conventional dendritic cells (DC) as a subset in neonatal skin specifically capable of uptake, presentation and generation of regulatory T cells (Tregs) to commensal antigens. In early life, CD301b+ DC2 are enriched for programs of phagocytosis and maturation, while also expressing tolerogenic markers. In both human and murine skin, these signatures were reinforced by microbial uptake. In contrast to their adult counterparts or other early life DC subsets, neonatal CD301b+ DC2 highly expressed the retinoic acid-producing enzyme, RALDH2, deletion of which limited commensal-specific Tregs. Thus, synergistic interactions between bacteria and a specialized DC subset critically support early life tolerance at the cutaneous interface.

ORGANISM(S): Mus musculus

PROVIDER: GSE217891 | GEO | 2023/01/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Neonatal foreskin antigen presenting cells after colonization with Staphylococcus epidermidis

Project description:Early life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here we show that this process is controlled by microbial interaction with a specialized subset of antigen presenting cells. More particularly, we identify CD301b+ type 2 conventional dendritic cells (DC) as a subset in neonatal skin specifically capable of uptake, presentation and generation of regulatory T cells (Tregs) to commensal antigens. In early life, CD301b+ DC2 are enriched for programs of phagocytosis and maturation, while also expressing tolerogenic markers. In both human and murine skin, these signatures were reinforced by microbial uptake. In contrast to their adult counterparts or other early life DC subsets, neonatal CD301b+ DC2 highly expressed the retinoic acid-producing enzyme, RALDH2, deletion of which limited commensal-specific Tregs. Thus, synergistic interactions between bacteria and a specialized DC subset critically support early life tolerance at the cutaneous interface.

2023-01-01 | GSE206893 | GEO

Skin and Skin Draining lymph node dendritic cells from neonatal mouse colonized with a commensal or control

2023-01-01 | GSE206892 | GEO

Mouse neonatal dendritic cells from uncolonized, and Staphylococcus epidermidis-zsgreen colonized mouse (loaded and non-loaded cells)

2023-01-01 | GSE206891 | GEO

A distinct human cell type expressing MHCII and RORγt with dual characteristics of dendritic cells and type 3 innate lymphoid cells

Project description:Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt, which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the autoimmune regulator AIRE. RORγt+ MHCII+ type 3 innate lymphoid cells (ILC3) have also been implicated in the instruction of microbiota specific Tregs. While RORγt+ APCs have been actively investigated in mice, the identity and function of these cell subsets in humans remain elusive. Herein, we identify a rare subset of RORγt+ cells with dendritic cell (DC) features through integrated single-cell RNA sequencing and single-cell ATAC sequencing. These cells, which we term RORγt+ DC-like cells (R-DC-like), exhibit DC morphology, express the MHC class II machinery, are distinct from all previously reported DC and ILC3 subsets, but share transcriptional and epigenetic similarities with DC2 and ILC3. We have developed procedures to isolate and expand them in vitro, enabling their functional characterization. R-DC-like cells proliferate in vitro, continue to express RORγt, and differentiate into CD1c+ DC2-like cells. They stimulate the proliferation of allogeneic T cells. The identification of human R-DC-like cells with proliferative potential and plasticity towards CD1c+ DC2-like cells will prompt further investigation into their impact on immune homeostasis, inflammation, and autoimmunity.

2023-12-19 | GSE247692 | GEO

TRANSITIONAL DENDRITIC CELLS ARE DISTINCT FROM CONVENTIONAL DC2 PRECURSORS AND MEDIATE PRO-INFLAMMATORY ANTIVIRAL RESPONSES

Project description:High-dimensional approaches revealed emerging heterogeneity within dendritic cells (DC), including a population of transitional DC (tDC) present in mouse and human. However, tDC origin and relationship to other DC subsets are not fully understood. Here, we show that tDC are distinct from other well-characterized DC and conventional DC precursors (pre-cDC). We demonstrate that tDC originate from bone marrow progenitors shared with plasmacytoid DC (pDC). In the periphery, tDC contribute to the pool of ESAM+ type 2 DC (DC2), and these DC2 harbor pDC-related developmental features. Different from pre-cDC, tDC have lower turnover, capture antigen, respond to stimuli, and activate antigen-specific naïve T cells, all characteristics of differentiated DC. Different from pDC, viral sensing by tDC results in IL-1b secretion and fatal immune pathology in a murine coronavirus model. Our findings suggest that tDC are a distinct pDC-related subset with a DC2 differentiation potential and unique pro-inflammatory function during viral infections.

2023-05-21 | GSE198553 | GEO

Gut bacteria-derived serotonin promotes immune tolerance in early life through regulation of neonatal gut T cells III

Project description:The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remains largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin; specific gut bacteria produce serotonin directly while downregulating monoamine oxidase A to limit serotonin breakdown. Serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye to inhibit mTOR activation and thereby promotes the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice leads to long-term T cell-mediated antigen-specific immune tolerance towards both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for unique gut bacteria to increase serotonin availability in the neonatal gut and a novel function of gut serotonin to shape T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.

2024-01-31 | GSE248692 | GEO

Gut bacteria-derived serotonin promotes immune tolerance in early life through regulation of neonatal gut T cells II

2024-01-31 | GSE248691 | GEO

Gut bacteria-derived serotonin promotes immune tolerance in early life through regulation of neonatal gut T cells I

2024-01-31 | GSE248690 | GEO

Type 2 cytokines in the thymus activate Sirpa+ dendritic cells to promote clonal deletion

Project description:The thymus contains a diversity of dendritic cells (DC) that exist in defined locations and have different antigen processing and presenting features. This suggests that they play non-redundant roles in mediating thymocyte selection. In an effort to eliminate SIRP+ cDC2, we discovered that a substantial proportion expresses the surface lectin, CD301b, in the thymus. These cells resemble the CD301b+ type 2 immune response promoting DC that are present in the skin draining lymph nodes. Transcriptional and phenotypic comparison to other DC subsets in the thymus revealed that thymic CD301b+ cDC represent an activated state that exhibits enhanced antigen processing and presentation. Furthermore, CD301b+ cDC2 demonstrated a type 2 cytokine signature and required steady state IL-4 receptor signaling. Selective ablation of CD301b+ cDC2 impaired clonal deletion without affecting regulatory T cells. TCR alpha repertoire sequencing confirmed that cDC2 promote deletion of conventional T cells with minimal effect on regulatory T cell selection. Together, these findings suggest that cytokine-induced activation of DC in the thymus substantially enforces central tolerance.

2022-03-23 | GSE198789 | GEO

Type 2 cytokines in the thymus activate Sirpa+ dendritic cells to promote clonal deletion

2022-05-09 | GSE198247 | GEO