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IL-21 Producing Effector Tfh Cells Promote B Cell Alloimmunity in Lymph Nodes and Kidney Allografts

ABSTRACT: IL-21 Producing Effector Tfh Cells Promote B Cell Alloimmunity in Lymph Nodes and Kidney Allografts

PROVIDER: PRJNA1006682 | ENA |

REPOSITORIES: ENA

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IL-21 Producing Effector Tfh Cells Promote B Cell Alloimmunity in Lymph Nodes and Kidney Allografts

Project description:Follicular helper T (Tfh) cells have been implicated in controlling rejection after allogeneic kidney transplantation, but the precise subsets, origins and functions of Tfh cells in this process have not been fully characterized. Here we show that a subset of effector Tfh cell marked by previous IL- 21 production is potently induced during allogeneic kidney transplantation and is inhibited by immunosuppressive agents. Single-cell RNAseq revealed that these lymph node effector Tfh cells have transcriptional and clonal overlap with IL-21 producing kidney infiltrating Tfh cells, implicating common origins and developmental trajectories. To investigate the precise functions of IL-21 producing effector Tfh cells in lymph nodes and allografts, we used a mouse model to selectively eliminate these cells and assessed allogeneic B cell clonal dynamics using a single B cell culture system. We found that IL-21 producing effector Tfh cells were essential for transplant rejection by regulating donor-specific germinal center B cell clonal dynamics both systemically in the draining lymph node and locally within kidney grafts. Thus, IL-21 producing effector Tfh cells have multifaceted roles in antibody-mediated rejection after kidney transplantation by promoting B cell alloimmunity.

2023-10-23 | GSE241181 | GEO

IL-21-producing effector Tfh cells promote B cell alloimmunity in lymph nodes and kidney allografts.

Project description:Follicular helper T (Tfh) cells have been implicated in controlling rejection after allogeneic kidney transplantation, but the precise subsets, origins, and functions of Tfh cells in this process have not been fully characterized. Here we show that a subset of effector Tfh cells marked by previous IL-21 production is potently induced during allogeneic kidney transplantation and is inhibited by immunosuppressive agents. Single-cell RNA-Seq revealed that these lymph node (LN) effector Tfh cells have transcriptional and clonal overlap with IL-21-producing kidney-infiltrating Tfh cells, implicating common origins and developmental trajectories. To investigate the precise functions of IL-21-producing effector Tfh cells in LNs and allografts, we used a mouse model to selectively eliminate these cells and assessed allogeneic B cell clonal dynamics using a single B cell culture system. We found that IL-21-producing effector Tfh cells were essential for transplant rejection by regulating donor-specific germinal center B cell clonal dynamics both systemically in the draining LN and locally within kidney grafts. Thus, IL-21-producing effector Tfh cells have multifaceted roles in Ab-mediated rejection after kidney transplantation by promoting B cell alloimmunity.

| S-EPMC10619486 | biostudies-literature

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)

2022-09-01 | E-MTAB-11644 | biostudies-arrayexpress

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)

| PRJEB52336 | ENA

Expression data from BCL6-YFP-positive Tfh cells, BCL6-YFP-negative Tfh cells, non-Tfh cells, and naïve helper T cells.

Project description:We found that a number of Tfh cells downmodulated BCL6 protein after their development, and we sought to compare the gene expression between BCL6-hi Tfh cells and BCL6-low Tfh cells. CD4+ T cells were sorted from immunized and non-immunized mice for RNA extraction and hybridization on Affymetrix microarrays. Bcl6yfp/+ OT-II cells were transferred to congenic recipient mice, and immunized with NP-OVA in CFA subcutaneously. Seven or ten days after immunization, cells were collected from draining lymph nodes, and sorted on FACSAria by the expression of CXCR5, PD-1 and BCL6-YFP. Naive CD4+ T cells were CD4+ CD44lo CD62Lhi cells from unimmunized mice.

2011-06-02 | E-GEOD-24574 | biostudies-arrayexpress

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.

2018-04-18 | GSE113250 | GEO

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.

2018-04-18 | GSE113249 | GEO

Lymph nodes with follicular lymphoma or reactive hyperplasia

Project description:Comparison of gene expression profiles of follicular lymphoma vs. reactive lymph nodes. 8 cases of follicular lymphoma; 5 cases of reactive lymph nodes.

2011-09-26 | E-GEOD-14214 | biostudies-arrayexpress

Expression data from pig mesenteric lymph nodes

Project description:The mesenteric lymph nodes represent the immune response to eggs in schistosome infections,and the analysis of gene expression profiles of the mesenteric lymph nodes from the Vac-Cha (vaccinated with UV attenuated cercariae and challenged with normal cercariae)and Inf-Con (infected with normal cercariae) groups. We used microarrays to detail the global programme of gene expression and identified distinct classes of up-regulated and down-regulated genes.

2010-06-11 | GSE22311 | GEO

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.

2016-05-26 | GSE74102 | GEO

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