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Resident regulatory T cells reflect the immune history of individual lymph nodes

ABSTRACT: Resident regulatory T cells reflect the immune history of individual lymph nodes

PROVIDER: PRJNA986930 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25010267.fastq.gz	Fastqsanger.gz
	SRR25010268.fastq.gz	Fastqsanger.gz
	SRR25010269.fastq.gz	Fastqsanger.gz
	SRR25010270.fastq.gz	Fastqsanger.gz
	SRR25010271.fastq.gz	Fastqsanger.gz

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Resident regulatory T cells reflect the immune history of individual lymph nodes

Project description:Regulatory T cells (Treg) are present in lymphoid and non-lymphoid tissues where they restrict immune activation, prevent autoimmunity and regulate inflammation. Treg in non-lymphoid tissues are typically resident, while those in lymph nodes (LNs) are considered to recirculate. However, Treg in LNs are not a homogenous population and circulation kinetics of different Treg subsets are poorly characterized. Furthermore, whether Treg can acquire memory T cell properties and persist for extended periods after their activation in LNs is unclear. Here, we used in situ labeling with a stabilized photoconvertible protein to uncover turnover rates of Treg in LNs in vivo. We found that while the majority of Treg in LNs recirculate, 10-20% are memory-like resident cells that remain in their respective LNs for weeks to months. Single cell RNA sequencing revealed that LN-resident cells are a functionally and ontogenetically heterogeneous population and share the same core residency gene signature with conventional CD4+ and CD8+ T cells. Resident cells in LNs did not actively proliferate and did not require continuous TCR signaling for their residency. Yet, resident and circulating Treg had distinct TCR repertoires, and each LN contained exclusive clonal subpopulations of resident Treg. Our results demonstrate that, similar to conventional T cells, Treg can form resident memory-like populations in LNs after adaptive immune responses. Specific and local suppression of immune responses by resident Treg in draining LNs might provide new therapeutic opportunities for the treatment of local chronic inflammatory conditions.

2023-08-23 | GSE235702 | GEO

scRNAseq of stromal cells isolated from mesenteric lymph nodes (MLN), peripheral lymph nodes (PLN) and mandibular lymph nodes (mandLN)

Project description:scRNAseq of stromal cells isolated from mesenteric lymph nodes (MLN), peripheral lymph nodes (PLN) and mandibular lymph nodes (mandLN)

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scRNAseq of stromal cells isolated from mesenteric lymph nodes (MLN), peripheral lymph nodes (PLN) and mandibular lymph nodes (mandLN)

Project description:scRNAseq of stromal cells isolated from mesenteric lymph nodes (MLN), peripheral lymph nodes (PLN) and mandibular lymph nodes (mandLN)

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Gene expression signatures for murine B cells from tumor-draining lymph nodes

Project description:To determine the influence of primary tumors on pre-metastatic lymph nodes, we have employed whole genome microarray expression profiling as a discovery platform to identify gene signatures of B cells from tumor-draining lymph nodes, compared with normal lymph nodes. We subcutaneously inoculated C57BL/6 mice with the 4T1 mammary carcinoma. Two weeks later, tumor-draining lymph nodes were dissociated and B cells (CD19+) were sorted. Lymph nodes B cells from normal mice without tumor bearing were set as controls.

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Gene expression signatures for murine stromal cells from tumor-draining lymph nodes

Project description:To determine the influence of primary tumors on pre-metastatic lymph nodes, we have employed whole genome microarray expression profiling as a discovery platform to identify gene signatures of stromal cells from tumor-draining lymph nodes, compared with normal lymph nodes. We subcutaneously inoculated C57BL/6 mice with the 4T1 mammary carcinoma. Two weeks later, tumor-draining lymph nodes were dissociated and stromal cells (CD45-) were sorted. Lymph nodes stromal cells from normal mice without tumor bearing were set as controls.

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Lymph nodes with follicular lymphoma or reactive hyperplasia

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Transcription Profiles of Regulatory T Cells in Follicular Lymphoma Lymph Nodes, Normal Lymph Nodes and Reactive Lymph Nodes

Project description:We have previously shown that Tregs infiltrating follicular lymphoma lymph nodes (FLN) are quantitatively and qualitatively different than those infiltrating normal and reactive nodes (NLN, RLN, respectively). To gain insight into how such Treg populations differ, we performed RNA sequence (RNAseq) analyses on flow sorted Tregs from all three sources. We identify several molecules that could contribute to the observed increased suppressive capacity of FLN tregs, including upregulation of CTLA-4, IL-10, and GITR, all confirmed by protein expression. In addition, we identify, and confirm functionally, a novel mechanism by which Tregs target to and accumulate within a human tumor microenvironment, through the down regulation of S1PR1, SELL (L-selectin) and CCR7, potentially resulting in greater lymph node retention. In addition we identify and confirm functionally the upregulation of CXCR5, CXCL13 and IL-16 demonstrating the unique ability of the follicular derived Tregs to localize and accumulate within not only the malignant lymph node, but also localize and accumulate within the malignant B cell follicle itself. Such findings offer significant new insights into how FLN Tregs may contribute to the biology of follicular lymphoma and identify several novel therapeutic targets.

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