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

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

PROVIDER: PRJNA852579 | ENA |

REPOSITORIES: ENA

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

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 | GSE206892 | GEO

Cytokine and receptor expression in skin draining lymph nodes after skin immunization

Project description:Topical (epicutaneous, e.c.) application of the adjuvant CpG ODN during immunization leads to a robust immune response compared to when subcutaneous (s.c.) administration. Dendritic cells are hematopoietically derived cells that are important in cross-presenting to and activating CD8 T cells. Dermal dendritic cells are one of the two major dendritic cell subsets found in the skin which mobilize from the skin to draining lymph nodes to present to T cells upon activation. Dermal dendritic cells are found in skin draining lymph nodes around 24 hours post immunization. To determine how the immune system respond differently between e.c. versus s.c. administration of CpG ODN, we evaluated changes in the skin draining lymph node environment upon the two routes of adjuvant application. Expression chemokines and chemokine receptors were assessed with real-time qPCR. To determine the changes in the skin draining lymph node environment (cytokine and cytokine receptor levels) upon immunization via real time RT-PCR.

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Project description:Purpose: To identify the presence of endogenous tumor-specific TRM cells in LNs, scRNAseq was performed to identify populations of CD8 T cells with TRM transcriptional characteristics in DLNs. Methods: CD8+CD44+ T cells were sorted from DLN and skin of MAV mice and scRNA-seq in parallel with scTCR-seq was performed. Results: The twenty most expanded clonotypes identified in vitiligo-affected skin of these mice, eight matched to lymph nodes and strikingly, those lymph node clonotypes that had matches in skin mapped almost exclusively to the LN TRM cluster Conclusions: Endogenous tumor-specific CD8 T cells form TRM responses in tumor-draining LNs.

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Project description:Cytokine and receptor expression in skin draining lymph nodes after skin immunization

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P14 T cells from C57BL6J draining lymph node after vaccinia-GP33

Project description:CD90.1 T cells were isolated from draining lymph nodes of vaccinia-GP33 infected ears 45 days post infection

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Gene expression signatures for B cells from tumor draining lymph node and normal lymph node

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Papillomavirus-Colonized Murine Skin Confers Cancer Resistance

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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.

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

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