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Enhancement of Human B Cell Differentiation and Function in Lymph Nodes by the TLR9 Agonist MGN1703

ABSTRACT: Enhancement of Human B Cell Differentiation and Function in Lymph Nodes by the TLR9 Agonist MGN1703

PROVIDER: PRJNA535447 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8955440_1.fastq.gz	Fastqsanger.gz
	SRR8955440_2.fastq.gz	Fastqsanger.gz
	SRR8955450_1.fastq.gz	Fastqsanger.gz
	SRR8955450_2.fastq.gz	Fastqsanger.gz
	SRR8955441_1.fastq.gz	Fastqsanger.gz

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Enhancement of Human B Cell Differentiation and Function in Lymph Nodes by the TLR9 Agonist MGN1703

Project description:TLR9 agonists are being developed as immunotherapies to increase immune effector cell activity against malignancies and pathogens. However, the in vivo impacts of TLR9 agonism on human B cells are incompletely known and the impacts of such treatments on human lymph node B cells are unknown. These are major knowledge gaps given the high TLR9 expression levels in B cells and the importance of lymph nodes for B cell activity. Therefore, we assessed TLR9 agonist-mediated effects on lymph node B cells as planned secondary endpoints within our clinical trial dosing the TLR9 agonist MGN1703 (Lefitolimod) in the context of developing an HIV cure strategy (NCT02443935).

2019-07-30 | GSE130307 | GEO

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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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Stimulation of isolated plasmacytoid dendritic cells (pDCs) with TLR9 agonist CpG C (CpG) and TLR7 agonist imiquimod (IMQ)

Project description:The purpose of this experiment was to assess the genes upregulated when pDCs were stimulated with TLR7 agonist imiquimod and TLR9 agonist CpG C.

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Stimulation of isolated plasmacytoid dendritic cells (pDCs) with TLR9 agonist CpG C (CpG) and TLR7 agonist imiquimod (IMQ)

Project description:The purpose of this experiment was to assess the genes upregulated when pDCs were stimulated with TLR7 agonist imiquimod and TLR9 agonist CpG C. pDCs were isolated from six healthy donors by FACS sorting, and were stimulated with CpG and imiquimod for 18 hours, after which RNA was extracted for next generation sequencing on the Illumina HiSeq platform. Unstimulated samples were included as controls.

2016-03-17 | E-GEOD-79272 | biostudies-arrayexpress

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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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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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Lymph nodes with follicular lymphoma or reactive hyperplasia

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TLR9 agonist MGN1703 enhances B cell differentiation and function in lymph nodes.

Project description:BackgroundTLR9 agonists are being developed as immunotherapy against malignancies and infections. TLR9 is primarily expressed in B cells and plasmacytoid dendritic cells (pDCs). TLR9 signalling may be critically important for B cell activity in lymph nodes but little is known about the in vivo impact of TLR9 agonism on human lymph node B cells. As a pre-defined sub-study within our clinical trial investigating TLR9 agonist MGN1703 (lefitolimod) treatment in the context of developing HIV cure strategies (NCT02443935), we assessed TLR9 agonist-mediated effects in lymph nodes.MethodsParticipants received MGN1703 for 24 weeks concurrent with antiretroviral therapy. Seven participants completed the sub-study including lymph node resection at baseline and after 24 weeks of treatment. A variety of tissue-based immunologic and virologic parameters were assessed.FindingsMGN1703 dosing increased B cell differentiation; activated pDCs, NK cells, and T cells; and induced a robust interferon response in lymph nodes. Expression of Activation-Induced cytidine Deaminase, an essential regulator of B cell diversification and somatic hypermutation, was highly elevated. During MGN1703 treatment IgG production increased and antibody glycosylation patterns were changed.InterpretationOur data present novel evidence that the TLR9 agonist MGN1703 modulates human lymph node B cells in vivo. These findings warrant further considerations in the development of TLR9 agonists as immunotherapy against cancers and infectious diseases. FUND: This work was supported by Aarhus University Research Foundation, the Danish Council for Independent Research and the NovoNordisk Foundation. Mologen AG provided study drug free of charge.

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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.

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