Induction of Indoleamine 2, 3-Dioxygenase in Human Dendritic Cells by a Cholera Toxin B Subunit—Proinsulin Vaccine
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{"title"=>"Induction of Indoleamine 2, 3-Dioxygenase in Human Dendritic Cells by a Cholera Toxin B Subunit—Proinsulin Vaccine", "type"=>"journal", "authors"=>[{"first_name"=>"Jacques C.", "last_name"=>"Mbongue"}, {"first_name"=>"Dequina A.", "last_name"=>"Nicholas"}, {"first_name"=>"Kangling", "last_name"=>"Zhang"}, {"first_name"=>"Nan-Sun", "last_name"=>"Kim"}, {"first_name"=>"Brittany N.", "last_name"=>"Hamilton"}, {"first_name"=>"Marco", "last_name"=>"Larios"}, {"first_name"=>"Guangyu", "last_name"=>"Zhang"}, {"first_name"=>"Kazuo", "last_name"=>"Umezawa"}, {"first_name"=>"Anthony F.", "last_name"=>"Firek"}, {"first_name"=>"William H. R.", "last_name"=>"Langridge"}], "year"=>2015, "source"=>"PLOS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84923876450", "sgr"=>"84923876450", "issn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0118562", "pmid"=>"25714914", "pui"=>"602543189"}, "id"=>"d182fdb2-d089-3e1f-97ee-f6df3e09c364", "abstract"=>"Dendritic cells (DC) interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1). Increased biosynthesis of the immunosuppressive enzyme was detected in DCs inoculated with the CTB-INS fusion protein but not in DCs inoculated with proinsulin, CTB, or an unlinked combination of the two proteins. Immunoblot and PCR analyses of vaccine treated DCs detected IDO1mRNA by 3 hours and IDO1 protein synthesis by 6 hours after vaccine inoculation. Determination of IDO1 activity in vaccinated DCs by measurement of tryptophan degradation products (kynurenines) showed increased tryptophan cleavage into N-formyl kynurenine. Vaccination did not interfere with monocytes differentiation into DC, suggesting the vaccine can function safely in the human immune system. Treatment of vaccinated DCs with pharmacological NF-κB inhibitors ACHP or DHMEQ significantly inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in vaccine up-regulation of dendritic cell IDO1. Heat map analysis of the proteomic data revealed an overall down-regulation of vaccinated DC functions, suggesting vaccine suppression of DC maturation. Together, our experimental data indicate that CTB-INS vaccine induction of IDO1 biosynthesis in human DCs may result in the inhibition of DC maturation generating a durable state of immunological tolerance. Understanding how CTB-INS modulates IDO1 activity in human DCs will facilitate vaccine efficacy and safety, moving this immunosuppressive strategy closer to clinical applications for prevention of type 1 diabetes autoimmunity.", "link"=>"http://www.mendeley.com/research/induction-indoleamine-2-3dioxygenase-human-dendritic-cells-cholera-toxin-b-subunitproinsulin-vaccine", "reader_count"=>12, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Brazil"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1924789"], "description"=>"<p>Flow cytometric analysis of vaccinated monocyte differentiation into dendritic cells. <b>(A)</b> The CD14 monocyte marker becomes progressively less positive (number inside the box (gate), as DC differentiation proceeds in the presence of the CTB-INS fusion protein. <b>(B)</b> The HLA-DR marker indicative of antigen presenting cell DC morphogenesis increases as dendritic cell differentiation progresses in the presence of CTB-INS. <b>(C)</b> The co-stimulatory factor marker for DC maturation CD86 is observed to decrease with time in vaccinated DCs in comparison with background levels. <b>(D)</b> With time after inoculation with CTB-INS, the dendritic cell marker CD83 indicative of DC maturation decreases in comparison with unvaccinated DC background levels.</p>", "links"=>[], "tags"=>["cholera toxin B subunit", "IDO 1 protein synthesis", "dhmeq", "pcr", "type 1 diabetes autoimmunity", "chimeric fusion protein vaccine", "tryptophan degradation products", "nf", "ctb", "DCs inoculated", "Human Dendritic Cells", "vaccinated DCs", "ACHP", "dendritic cell IDO 1. Heat map analysis", "IDO 1 activity", "vaccinated DC functions", "DC maturation", "vaccine inoculated DCs", "ïve T cells", "IDO 1 biosynthesis"], "article_id"=>1318217, "categories"=>["Biological Sciences"], "users"=>["Jacques C. Mbongue", "Dequina A. Nicholas", "Kangling Zhang", "Nan-Sun Kim", "Brittany N. Hamilton", "Marco Larios", "Guangyu Zhang", "Kazuo Umezawa", "Anthony F. Firek", "William H. R. Langridge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118562.g006", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CTB_INS_vaccination_of_monocytes_does_not_interfere_with_dendritic_cell_differentiation_/1318217", "title"=>"CTB-INS vaccination of monocytes does not interfere with dendritic cell differentiation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-25 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1924774"], "description"=>"<p>(A) Venn diagram of significantly up or down regulated proteins in human monocyte derived dendritic cells inoculated with CTB-INS in comparison with monocytes as the baseline. A total of 845 proteins were identified in untreated DCs and 654 up and down-regulated proteins were unique in CTB-INS treated DCs, while 131 proteins were common to both treated and untreated DCs. (B) Canonical, metabolic and signaling pathways that correlate with changes in protein expression in CTB-INS vaccinated dendritic cells identified by IPA program analysis. The threshold line represents the value at which statistical significance is reported. The grey line connects the ratios between the number of up and down-regulated proteins over the total number of proteins identified in each of the pathways shown.</p>", "links"=>[], "tags"=>["cholera toxin B subunit", "IDO 1 protein synthesis", "dhmeq", "pcr", "type 1 diabetes autoimmunity", "chimeric fusion protein vaccine", "tryptophan degradation products", "nf", "ctb", "DCs inoculated", "Human Dendritic Cells", "vaccinated DCs", "ACHP", "dendritic cell IDO 1. Heat map analysis", "IDO 1 activity", "vaccinated DC functions", "DC maturation", "vaccine inoculated DCs", "ïve T cells", "IDO 1 biosynthesis"], "article_id"=>1318202, "categories"=>["Biological Sciences"], "users"=>["Jacques C. Mbongue", "Dequina A. Nicholas", "Kangling Zhang", "Nan-Sun Kim", "Brittany N. Hamilton", "Marco Larios", "Guangyu Zhang", "Kazuo Umezawa", "Anthony F. Firek", "William H. R. Langridge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118562.g001", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mass_spectrometric_identification_of_the_CTB_INS_vaccinated_DC_proteome_/1318202", "title"=>"Mass spectrometric identification of the CTB-INS vaccinated DC proteome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-25 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1924782"], "description"=>"<p><b>(A)</b> Dendritic cell viability was measured by determination of the percentage of DCs negative for annexin V and propidium iodide following treatment with ACHP (500 nM) and DHMEQ (3μg/ml). The measurement of DC viability shows vaccinated DCs are unaffected by treatment with the inhibitors. <b>(B, C)</b> Agarose gel electrophoresis and graphic representation showing changes in <i>IDO1</i> mRNA levels in DCs from three representative subjects determined by qRT-PCR after 3 hours incubation of subject monocyte derived DCs with CTB-INS (10 μg/mL) or CTB-INS and ACHP. Statistical significance (p<0.05) was achieved by analysis of a total of 5 subjects. (The vehicle used is the DMSO solvent in which ACHP and DHMEQ are dissolved). <b>(D, E)</b> Immunoblot and graphic representation of the fold change in IDO protein synthesized 24hrs after vaccine inoculation of subjects DCs inoculated with CTB-INS +/- ACHP. The experimental data was collected from five normal subjects, although only one representative subject is shown. Statistical significance between vaccine treated and vaccine + ACHP treated groups was measured by paired Student’s t test, (p = 0.0273). <b>(F, G)</b> Immunoblot and graphic representation of the fold change in IDO1 protein synthesized in subject DCs following inoculation with CTB-INS with and without DHMEQ. While experimental data was collected from five normal subjects, only two are shown to highlight the variability in IDO1 levels observed among subjects. Statistical significance was measured by paired Student’s t test (p = 0.017). <b>(H)</b> Graphic representation showing the relative efficacy of ACHP and DHMEQ inhibitors for blocking NF-κB induction of IDO1 biosynthesis.</p>", "links"=>[], "tags"=>["cholera toxin B subunit", "IDO 1 protein synthesis", "dhmeq", "pcr", "type 1 diabetes autoimmunity", "chimeric fusion protein vaccine", "tryptophan degradation products", "nf", "ctb", "DCs inoculated", "Human Dendritic Cells", "vaccinated DCs", "ACHP", "dendritic cell IDO 1. Heat map analysis", "IDO 1 activity", "vaccinated DC functions", "DC maturation", "vaccine inoculated DCs", "ïve T cells", "IDO 1 biosynthesis"], "article_id"=>1318210, "categories"=>["Biological Sciences"], "users"=>["Jacques C. Mbongue", "Dequina A. Nicholas", "Kangling Zhang", "Nan-Sun Kim", "Brittany N. Hamilton", "Marco Larios", "Guangyu Zhang", "Kazuo Umezawa", "Anthony F. Firek", "William H. R. Langridge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118562.g004", "stats"=>{"downloads"=>0, "page_views"=>41, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ACHP_and_DHMEQ_inhibitors_of_NF_954_B_block_CTB_INS_induced_IDO1_biosynthesis_/1318210", "title"=>"ACHP and DHMEQ inhibitors of NF-κB block CTB-INS induced IDO1 biosynthesis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-25 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1924777"], "description"=>"<p>(A) Heat map representing cellular functions (z-scores*) identified in vaccinated dendritic cells. Red bands indicate up-regulated cellular functions, yellow bands indicate no change in function and green bands indicate down-regulated cellular functions. (B) Principal component (PC) analysis of dendritic cell functions, z-scores. The Bi-plot correlates dendritic cell functions (+/-) vaccine treatments as indicated by the proximity of individual DC functions (numbers) to either vector arrowhead [a = CTB-INS (-), b = CTB-INS (+)]. Numbers further from the mean in the direction of the vector exhibit an increased correlation of the DC function with a or b. Example: Function #12 is highly correlated with unvaccinated DCs, [CTB-INS (-)] and Function #2 is poorly correlated with vaccinated DCs, [CTB-INS (+)]. Zero (0) is the weighted mean of the multivariate dataset. The values on the (x; y) axis represent (+/-) deviation from the mean of the dataset (0). (*z-score = statistical measurement of a score’s relationship to the mean in a group of scores. A z-score of 0 means the score is the same as the mean. A z-score can also be positive or negative, indicating whether it is above or below the mean and by how many standard deviations.)</p>", "links"=>[], "tags"=>["cholera toxin B subunit", "IDO 1 protein synthesis", "dhmeq", "pcr", "type 1 diabetes autoimmunity", "chimeric fusion protein vaccine", "tryptophan degradation products", "nf", "ctb", "DCs inoculated", "Human Dendritic Cells", "vaccinated DCs", "ACHP", "dendritic cell IDO 1. Heat map analysis", "IDO 1 activity", "vaccinated DC functions", "DC maturation", "vaccine inoculated DCs", "ïve T cells", "IDO 1 biosynthesis"], "article_id"=>1318205, "categories"=>["Biological Sciences"], "users"=>["Jacques C. Mbongue", "Dequina A. Nicholas", "Kangling Zhang", "Nan-Sun Kim", "Brittany N. Hamilton", "Marco Larios", "Guangyu Zhang", "Kazuo Umezawa", "Anthony F. Firek", "William H. R. Langridge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118562.g002", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CTB_INS_vaccine_induced_changes_in_DC_cellular_functions_/1318205", "title"=>"CTB-INS vaccine induced changes in DC cellular functions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-25 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1924794", "https://ndownloader.figshare.com/files/1924795", "https://ndownloader.figshare.com/files/1924796", "https://ndownloader.figshare.com/files/1924797", "https://ndownloader.figshare.com/files/1924798", "https://ndownloader.figshare.com/files/1924799"], "description"=>"<div><p>Dendritic cells (DC) interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1). Increased biosynthesis of the immunosuppressive enzyme was detected in DCs inoculated with the CTB-INS fusion protein but not in DCs inoculated with proinsulin, CTB, or an unlinked combination of the two proteins. Immunoblot and PCR analyses of vaccine treated DCs detected <i>IDO1</i>mRNA by 3 hours and IDO1 protein synthesis by 6 hours after vaccine inoculation. Determination of IDO1 activity in vaccinated DCs by measurement of tryptophan degradation products (kynurenines) showed increased tryptophan cleavage into N-formyl kynurenine. Vaccination did not interfere with monocytes differentiation into DC, suggesting the vaccine can function safely in the human immune system. Treatment of vaccinated DCs with pharmacological NF-κB inhibitors ACHP or DHMEQ significantly inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in vaccine up-regulation of dendritic cell IDO1. Heat map analysis of the proteomic data revealed an overall down-regulation of vaccinated DC functions, suggesting vaccine suppression of DC maturation. Together, our experimental data indicate that CTB-INS vaccine induction of IDO1 biosynthesis in human DCs may result in the inhibition of DC maturation generating a durable state of immunological tolerance. Understanding how CTB-INS modulates IDO1 activity in human DCs will facilitate vaccine efficacy and safety, moving this immunosuppressive strategy closer to clinical applications for prevention of type 1 diabetes autoimmunity.</p></div>", "links"=>[], "tags"=>["cholera toxin B subunit", "IDO 1 protein synthesis", "dhmeq", "pcr", "type 1 diabetes autoimmunity", "chimeric fusion protein vaccine", "tryptophan degradation products", "nf", "ctb", "DCs inoculated", "Human Dendritic Cells", "vaccinated DCs", "ACHP", "dendritic cell IDO 1. Heat map analysis", "IDO 1 activity", "vaccinated DC functions", "DC maturation", "vaccine inoculated DCs", "ïve T cells", "IDO 1 biosynthesis"], "article_id"=>1318222, "categories"=>["Biological Sciences"], "users"=>["Jacques C. Mbongue", "Dequina A. Nicholas", "Kangling Zhang", "Nan-Sun Kim", "Brittany N. Hamilton", "Marco Larios", "Guangyu Zhang", "Kazuo Umezawa", "Anthony F. Firek", "William H. R. Langridge"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0118562.s001", "https://dx.doi.org/10.1371/journal.pone.0118562.s002", "https://dx.doi.org/10.1371/journal.pone.0118562.s003", "https://dx.doi.org/10.1371/journal.pone.0118562.s004", "https://dx.doi.org/10.1371/journal.pone.0118562.s005", "https://dx.doi.org/10.1371/journal.pone.0118562.s006"], "stats"=>{"downloads"=>2, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induction_of_Indoleamine_2_3_Dioxygenase_in_Human_Dendritic_Cells_by_a_Cholera_Toxin_B_Subunit_8212_Proinsulin_Vaccine_/1318222", "title"=>"Induction of Indoleamine 2, 3-Dioxygenase in Human Dendritic Cells by a Cholera Toxin B Subunit—Proinsulin Vaccine", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-02-25 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1924791"], "description"=>"<p>Effect of CTB-INS on proteins associated with type 1 diabetes onset.</p>", "links"=>[], "tags"=>["cholera toxin B subunit", "IDO 1 protein synthesis", "dhmeq", "pcr", "type 1 diabetes autoimmunity", "chimeric fusion protein vaccine", "tryptophan degradation products", "nf", "ctb", "DCs inoculated", "Human Dendritic Cells", "vaccinated DCs", "ACHP", "dendritic cell IDO 1. Heat map analysis", "IDO 1 activity", "vaccinated DC functions", "DC maturation", "vaccine inoculated DCs", "ïve T cells", "IDO 1 biosynthesis"], "article_id"=>1318219, "categories"=>["Biological Sciences"], "users"=>["Jacques C. Mbongue", "Dequina A. Nicholas", "Kangling Zhang", "Nan-Sun Kim", "Brittany N. Hamilton", "Marco Larios", "Guangyu Zhang", "Kazuo Umezawa", "Anthony F. Firek", "William H. R. Langridge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118562.t002", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_CTB_INS_on_proteins_associated_with_type_1_diabetes_onset_/1318219", "title"=>"Effect of CTB-INS on proteins associated with type 1 diabetes onset.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-02-25 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1924790"], "description"=>"<p>Effect of CTB-INS on dendritic cell proteins associated with maturation and activation.</p>", "links"=>[], "tags"=>["cholera toxin B subunit", "IDO 1 protein synthesis", "dhmeq", "pcr", "type 1 diabetes autoimmunity", "chimeric fusion protein vaccine", "tryptophan degradation products", "nf", "ctb", "DCs inoculated", "Human Dendritic Cells", "vaccinated DCs", "ACHP", "dendritic cell IDO 1. Heat map analysis", "IDO 1 activity", "vaccinated DC functions", "DC maturation", "vaccine inoculated DCs", "ïve T cells", "IDO 1 biosynthesis"], "article_id"=>1318218, "categories"=>["Biological Sciences"], "users"=>["Jacques C. Mbongue", "Dequina A. Nicholas", "Kangling Zhang", "Nan-Sun Kim", "Brittany N. Hamilton", "Marco Larios", "Guangyu Zhang", "Kazuo Umezawa", "Anthony F. Firek", "William H. R. Langridge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118562.t001", "stats"=>{"downloads"=>0, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_CTB_INS_on_dendritic_cell_proteins_associated_with_maturation_and_activation_/1318218", "title"=>"Effect of CTB-INS on dendritic cell proteins associated with maturation and activation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-02-25 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1924785"], "description"=>"<p>Signaling pathways involved in vaccine up-regulation of IDO1 biosynthesis in human DCs were identified by Ingenuity Pathway analysis of proteins detected in vaccinated DCs by mass spectrometer analysis. (Red: up-regulation of the protein, Green: down-regulation of the protein, Grey: protein levels unchanged, White: Undetected). Based on calculations generated from the mass spectrometry data, the IPA program indicates the vaccine up-regulates the aryl hydrocarbon receptor (AhR) signal transduction pathways and down regulates TYROBP to increase IDO biosynthesis. <b>NF-κB1</b>: is the P105 precursor subunit of NF-κB which is cleaved to generate the P50 subunit of the canonical NF-κB transcriptional activator protein, located in the cytoplasm. <b>NF-κB2</b>: is the P100 subunit of non-canonical NF-κB, cleaved to generate the p52 subunit, located in the cytoplasm.</p>", "links"=>[], "tags"=>["cholera toxin B subunit", "IDO 1 protein synthesis", "dhmeq", "pcr", "type 1 diabetes autoimmunity", "chimeric fusion protein vaccine", "tryptophan degradation products", "nf", "ctb", "DCs inoculated", "Human Dendritic Cells", "vaccinated DCs", "ACHP", "dendritic cell IDO 1. Heat map analysis", "IDO 1 activity", "vaccinated DC functions", "DC maturation", "vaccine inoculated DCs", "ïve T cells", "IDO 1 biosynthesis"], "article_id"=>1318213, "categories"=>["Biological Sciences"], "users"=>["Jacques C. Mbongue", "Dequina A. Nicholas", "Kangling Zhang", "Nan-Sun Kim", "Brittany N. Hamilton", "Marco Larios", "Guangyu Zhang", "Kazuo Umezawa", "Anthony F. Firek", "William H. R. Langridge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118562.g005", "stats"=>{"downloads"=>0, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Diagram_of_upstream_signals_that_regulate_IDO1_biosynthesis_in_CTB_INS_vaccinated_human_DCs_/1318213", "title"=>"Diagram of upstream signals that regulate IDO1 biosynthesis in CTB-INS vaccinated human DCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-25 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1924779"], "description"=>"<p>(A) Immunoblot detection of IDO1 protein synthesis in human DCs in the presence of CTB-INS. <b>(B)</b> Immunoblot analysis of IDO1 up-regulation in DCs inoculated with all components of the CTB-INS fusion protein including insulin C-peptide. The images are representative of five subjects. <b>(C)</b> Reverse transcriptase polymerase chain reaction (RT-PCR) for assessment of <i>IDO1</i> mRNA expression in a time dependent manner from DCs incubated with and without CTB-INS. RNA (2 μg). The cDNA samples were used as templates for PCR amplification. The DNA amplification products were visualized on X ray film after electrophoresis in 2.0% agarose gels. <i>Lane M</i>: 100 bps DNA ladder marker (<i>Gibco</i>); <i>lane NC</i>: negative control RNA after treatment with DNase I from DCs as template; <i>lane 0</i>: cDNA from DCs without CTB-INS inoculation (-); <i>lanes 1</i>, <i>3</i>, <i>6</i>, <i>9</i>, <i>12 and 24</i>: cDNA from time-dependent DCs incubated with CTB-INS (+). A β-actin gene was used as an internal standard in RT-PCR.The image is representative of 3 different subjects. <b>(D, E)</b> Immunoblot of a time course of IDO1 expression in DCs after inoculation with CTB-INS (10μg/mL). Cell samples were harvested at 0, 3, 6, 8, 12 and 24 hours after vaccine inoculation. The data is representative of 6 different subject samples. (Shapes on Panel E represent different subjects). <b>(F, G)</b> Assessment of vaccine induced IDO1 activity and L-1-methyl-L-tryptophan (L-1-MT) inhibition of IDO1 activity in vaccinated DCs identified by ELISA. Top wells in the plate (F), show the production of tryptophan degradation products (kynurenines) in vaccinated DCs. Bottom wells show the inhibition of IDO1 kynurenine biosynthesis (absence of yellow color), in vaccinated DCs treated with L-1-MT (bottom wells). The data was compared for significance using a paired t-test, p = 0.018.</p>", "links"=>[], "tags"=>["cholera toxin B subunit", "IDO 1 protein synthesis", "dhmeq", "pcr", "type 1 diabetes autoimmunity", "chimeric fusion protein vaccine", "tryptophan degradation products", "nf", "ctb", "DCs inoculated", "Human Dendritic Cells", "vaccinated DCs", "ACHP", "dendritic cell IDO 1. Heat map analysis", "IDO 1 activity", "vaccinated DC functions", "DC maturation", "vaccine inoculated DCs", "ïve T cells", "IDO 1 biosynthesis"], "article_id"=>1318207, "categories"=>["Biological Sciences"], "users"=>["Jacques C. Mbongue", "Dequina A. Nicholas", "Kangling Zhang", "Nan-Sun Kim", "Brittany N. Hamilton", "Marco Larios", "Guangyu Zhang", "Kazuo Umezawa", "Anthony F. Firek", "William H. R. Langridge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118562.g003", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccine_induction_of_IDO1_biosynthesis_in_dendritic_cells_/1318207", "title"=>"Vaccine induction of IDO1 biosynthesis in dendritic cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-25 03:49:05"}

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  • {"unique-ip"=>"21", "full-text"=>"14", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"17", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
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  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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