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Recombinant human lactoferrin activates human dendritic cells via Toll-like receptors-2 and -4

ABSTRACT: Talactoferrin alfa (TLF) is a unique recombinant version of human lactoferrin, an important immunomodulatory protein present in exocrine secretions and in the secondary granules of neutrophils. Talactoferrin has demonstrated anti-cancer activity in preclinical studies and in Phase III clinical trials in patients with Renal Cell Cancer and non-small cell lung cancer. We have shown that TLF induces the maturation of human DCs derived from monocytes, suggesting that the linkage of the innate and adaptive immunity through DC maturation is a key immune function mediated by TLF. In this study we used genome-wide expression analysis to explore the mechanisms by which TLF leads to the functional maturation of DC. We show that GMP level recombinant TLF activates human DCs in a Toll-like receptor (TLR) -2 and -4 dependent manner.

ORGANISM(S): Homo sapiens

PROVIDER: GSE26438 | GEO | 2013/12/30

SECONDARY ACCESSION(S): PRJNA136819

REPOSITORIES: GEO

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Recombinant human lactoferrin activates human dendritic cells via Toll-like receptors-2 and -4

Project description:Talactoferrin alfa (TLF) is a unique recombinant version of human lactoferrin, an important immunomodulatory protein present in exocrine secretions and in the secondary granules of neutrophils. Talactoferrin has demonstrated anti-cancer activity in preclinical studies and in Phase III clinical trials in patients with Renal Cell Cancer and non-small cell lung cancer. We have shown that TLF induces the maturation of human DCs derived from monocytes, suggesting that the linkage of the innate and adaptive immunity through DC maturation is a key immune function mediated by TLF. In this study we used genome-wide expression analysis to explore the mechanisms by which TLF leads to the functional maturation of DC. We show that GMP level recombinant TLF activates human DCs in a Toll-like receptor (TLR) -2 and -4 dependent manner. Human peripheral blood mononuclear cells (PBMCs) were obtained from buffy coats of healthy donors. CD14+ cells were isolated from fresh PBMCs by positive immunoselection with magnetic beads. Immature dendritic cells (i-DC) from four donors were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. On day 6, cells were harvested in order to have iDC or mDC (conventionally matured DC) by addition of Tumor Necrosis Factor (TNF) -alfa and IL-1beta or TLF-DC (Talactoferrin matured DC) adding Food and Drug Administration-approved, GMP level recombinant TLF generated in eukaryotic cells. After 24 hour culture, cells were harvested and analyzed with Illumina arrays.

2013-12-30 | E-GEOD-26438 | biostudies-arrayexpress

RNA Sequencing Analysis of Mouse Bone Marrow Derived Dendritic Cells Transcriptomes During Maturation

Project description:Purpose:The purpose of this study is to detect activated or silenced genes during LPS-induced dendritic cell maturation. Gene expression differences between two samples could be found using transcriptome profiling (RNA-seq) analysis. Methods:Mouse dendritic cells were generated from bone marrow cells in RPMI-1640 medium with recombinant mouse GM-CSF and IL-4, mature DCs were obtained after LPS induced maturation. Immature DCs and mature DCs were sorted respectively based on maturation marker CD86 and Iab(MHCII) using flowcytrometer. DC mRNA profiles were generated by deep sequencing,using Illumina Results: We mapped about 10 million sequence reads per sample to the mouse genome, identified 1,300 upregulated genes and 1,475 dow regulated genes during dendritic cell maturation. DC mRNA profiles immature and mature moouse BMDCs were generated by deep sequencing

2015-03-04 | E-GEOD-60307 | biostudies-arrayexpress

Effect of lactoferrin treatment on iAEC2

Project description:In an attempt to understand the mode of antiviral action of lactoferrin on SARS-CoV-2 infection, we focused on the effect of lactoferrin on uninfected cells. We decided to use a physiologically relevant cell model of iPSC derived- alveolar epithelial cells (the iAEC2). We specifically focused on antiviral pathway triggered by lactoferrin on treated cells that could explain a cell-mediated effect of lactoferrin on viral replication

2021-07-15 | GSE171390 | GEO

Effects of lactoferrin, sophorolipids and lactoferrin-sophorolipids-assembly on gene expression of human dermal fibroblasts (HDFn)

Project description:The aim of this study is investigate effects of lactoferrin on human dermal fibroblasts and if sophorolipids influence effects of lactoferrin on human dermal fibroblasts.

2016-07-08 | GSE84144 | GEO

Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions [CEBPbetaKO]

Project description:Dendritic cell (DC) maturation is a prerequisite for the induction of adaptive immune responses against pathogens and cancer. Transcription factor (TF) networks control differential aspects of early DC progenitor versus late stage DC cell fate decisions. Here, we identified the TF C/EBPβ as a key regulator for DC maturation and immunogenic functionality under homeostatic and lymphoma-transformed conditions. Gene expression profiles of splenic C/EBPβ-/- DCs showed a strong downregulation of E2F cell cycle target genes, whereas signatures of maturation were enriched. In accordance with E2F1 being a negative regulator of DC maturation, C/EBPβ-/- bone marrow-derived DCs matured much faster enabling them to strongly activate T cells. Conversely, the E2F transcriptional pathways were upregulated in lymphoma-exposed DCs and DC maturation was impaired. Pharmacological blockade of C/EBPβ/mTOR signaling in human DCs abrogated their pro-tumorigenic function in B-cell lymphoma co-cultures. Thus, C/EBPβ plays a unique role in DC maturation and functionality and emerges as a key factor of the microenvironment promoting lymphomagenesis.

2020-10-20 | GSE123591 | GEO

Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions [Emu-Myc]

2020-10-20 | GSE123592 | GEO

Cdc42 controls DC-maturation - Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells

Project description:Cell division cycle 42 (Cdc42) is a member of the Rho GTPase family and has pivotal functions in actin organization, cell migration and proliferation. Cdc42 has been shown to regulate antigen (Ag)-uptake in immature dendritic cells (DC) and controls their migration from tissues to lymph nodes. Previous reports demonstrated that Cdc42 is inactivated upon DC-maturation to avoid continued Ag-acquisition. To further study the molecular mechanisms of DC-control by Cdc42, we used bone marrow-derived DCs from Cdc42-deficient mice. We show that Cdc42-deficient DCs are phenotypically mature without additional maturation stimuli, as they upregulate CD86 from intracellular storages to the cell surface. They also accumulate invariant chain (Ii)-MHC class II complexes at the cell surface, which cannot efficiently present peptide Ag for priming of Ag-specific CD4 T cells. Lack of Cdc42 in immature DCs does not allow MHC class II maturation, as lysosomal Cathepsins are lost into the supernatant and Ii-MHC class II complexes cannot mature. Therefore Cdc42-deficient DCs are "pseudomature" and lose most functional hallmarks of antigen-presenting cells. Our results propose that Cdc42 keeps DCs in an immature state, while downregulation of Cdc42-activity during maturation facilitates generation of CD86+MHCII+ mature DCs.

2015-10-12 | PXD001934 | Pride

RNA Sequencing Analysis of Mouse Bone Marrow Derived Dendritic Cells Transcriptomes During Maturation

2015-03-04 | GSE60307 | GEO

Caco2 response to methotrexate, lactoferrin, and methotrexate-lactoferrin co-exposure

Project description:Caco2 response to methotrexate, lactoferrin, and methotrexate-lactoferrin co-exposure

| PRJNA588171 | ENA

Proteome and phophoproteome analysis of distinct dendritic cell maturation states

Project description:Depending on their environment and their exposure to various factors, dendritic cells (DCs) exist in different activation and maturation states. The versatility of DCs allows them to shape the immune system towards an inflammatory or tolerant state depending on the antigens and the environment they encounter. In this study we aimed to provide a proteomic catalogue of differentially expressed and differentially phosphorylated proteins between distinct DC maturation states, brought about by bacteria that differ in their endotoxicity. To achieve this, we have performed unlabeled shotgun proteomics and phosphoproteomics on cell fractions obtained from murine bone marrow DC cultures. The symbiont B. vulgatus stimulation was used to obtain semi-mature DCs, and the pathobiont E. coli stimulation was used to obtain mature DCs. For both shotgun proteome and phosphoproteome analysis two biological replicates consisting of 8 mice were used. Each biological replicate were run as 3 technical replicates.

2017-11-27 | PXD003738 | Pride

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