A Novel CMKLR1 Small Molecule Antagonist Suppresses CNS Autoimmune Inflammatory Disease
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{"title"=>"A novel CMKLR1 small molecule antagonist suppresses CNS autoimmune inflammatory disease", "type"=>"journal", "authors"=>[{"first_name"=>"Kareem L.", "last_name"=>"Graham", "scopus_author_id"=>"7201360205"}, {"first_name"=>"Jian V.", "last_name"=>"Zhang", "scopus_author_id"=>"56449625000"}, {"first_name"=>"Susanna", "last_name"=>"Lewén", "scopus_author_id"=>"23479901400"}, {"first_name"=>"Thomas M.", "last_name"=>"Burke", "scopus_author_id"=>"56305814200"}, {"first_name"=>"Ton", "last_name"=>"Dang", "scopus_author_id"=>"56450231400"}, {"first_name"=>"Maria", "last_name"=>"Zoudilova", "scopus_author_id"=>"17344766600"}, {"first_name"=>"Raymond A.", "last_name"=>"Sobel", "scopus_author_id"=>"7102555142"}, {"first_name"=>"Eugene C.", "last_name"=>"Butcher", "scopus_author_id"=>"7102193127"}, {"first_name"=>"Brian A.", "last_name"=>"Zabel", "scopus_author_id"=>"7006015583"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84918837762", "pui"=>"600628468", "doi"=>"10.1371/journal.pone.0112925", "issn"=>"19326203", "pmid"=>"25437209", "sgr"=>"84918837762"}, "id"=>"5a7c1c84-1d3e-34bb-8d06-29bc404c406e", "abstract"=>"Therapies that target leukocyte trafficking pathways can reduce disease activity and improve clinical outcomes in multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) is a widely studied animal model that shares many clinical and histological features with MS. Chemokine-like receptor-1 (CMKLR1) is a chemoattractant receptor that is expressed by key effector cells in EAE and MS, including macrophages, subsets of dendritic cells, natural killer cells and microglia. We previously showed that CMKLR1-deficient (CMKLR1 KO) mice develop less severe clinical and histological EAE than wild-type mice. In this study, we sought to identify CMKLR1 inhibitors that would pharmaceutically recapitulate the CMKLR1 KO phenotype in EAE. We identified 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-NETA) as a CMKLR1 small molecule antagonist that inhibits chemerin-stimulated β-arrestin2 association with CMKLR1, as well as chemerin-triggered CMKLR1+ cell migration. α-NETA significantly delayed the onset of EAE induced in C57BL/6 mice by both active immunization with myelin oligodendrocyte glycoprotein peptide 35-55 and by adoptive transfer of encephalitogenic T cells. In addition, α-NETA treatment significantly reduced mononuclear cell infiltrates within the CNS. This study provides additional proof-of-concept data that targeting CMKLR1:chemerin interactions may be beneficial in preventing or treating MS.", "link"=>"http://www.mendeley.com/research/novel-cmklr1-small-molecule-antagonist-suppresses-cns-autoimmune-inflammatory-disease", "reader_count"=>26, "reader_count_by_academic_status"=>{"Researcher"=>8, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>2, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Researcher"=>8, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>2, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>13, "Medicine and Dentistry"=>2, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>3, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>1}, "Psychology"=>{"Psychology"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Italy"=>1, "United Kingdom"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1811795"], "description"=>"<p>(A) Brain and spinal cord tissues were harvested 16 days after active EAE induction from mice treated with α-NETA or vehicle control. Histological changes in meninges (<i>left panel</i>) and parenchyma (<i>right panel</i>) were evaluated as described in <i>Materials and Methods</i>. Results are pooled from two independent experiments with similar results, each with 4–6 mice per group. mean ± SEM, *<i>p</i><0.05 as by Student's <i>t</i> test. (B) Representative spinal cord sections are shown from actively immunized vehicle- (<i>left panel</i>) or α-NETA- (<i>right panel</i>) treated mice that were euthanized at 16 days p.i. Meningeal and parenchymal mononuclear cell infiltrates typical of acute EAE in the spinal cord of a vehicle-treated mouse (<i>left panel</i>). Less meningeal and parenchymal infiltration, as well as reduced myelin loss (indicated by Luxol fast blue staining intensity), in the spinal cord of α-NETA-treated mice with EAE (<i>right panel</i>). Bar, 50 µm. (C) At day 16 p.i., mononuclear cells isolated from the CNS and spleen of EAE mice treated with α-NETA or vehicle control were enumerated by flow cytometry. n = 7 mice/group; mean ± SEM; *<i>p</i><0.05 by Student's <i>t</i> test. (D) CNS mononuclear cells were isolated at day 16 p.i. from EAE mice treated with α-NETA or vehicle control. Cells were then stained with fluorophore-labeled monoclonal antibodies to identify the indicated leukocyte subsets: T cells (CD3+), B cells (B220+), dendritic cells (DC; CD3-B220-NK1.1-CD11c+) and macrophages (Mac; F4/80+CD11b+). *<i>p</i><0.05 by Student's <i>t</i> test. Two independent experiments yielded similar results.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256032, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.g004", "stats"=>{"downloads"=>2, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reduced_histological_EAE_in_945_NETA_treated_mice_/1256032", "title"=>"Reduced histological EAE in α-NETA-treated mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811808"], "description"=>"a<p>Data are pooled from two independent experiments with each experiment consisting of 7–8 mice per group.</p>b<p>Determined only for animals that developed EAE.</p>ns<p>: not significant (p = 0.18) by Students <i>t</i> test for mean day of onset or by Fisher's exact test for day 20 incidence (p = 0.06).</p><p>Clinical EAE in actively immunized CMKLR1 KO mice treated with α-NETA<sup><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112925#nt126\" target=\"_blank\">a</a></sup>.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256045, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.t007", "stats"=>{"downloads"=>1, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_EAE_in_actively_immunized_CMKLR1_KO_mice_treated_with_NETA_a_/1256045", "title"=>"Clinical EAE in actively immunized CMKLR1 KO mice treated with α-NETA<sup>a</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811807"], "description"=>"a<p>Data are pooled from two independent experiments with each experiment consisting of 5–6 mice per group.</p>b<p>Determined only for animals that developed EAE.</p><p>*p<0.05 as determined by Students <i>t</i> test;</p>†<p>p<0.05, as determined by Fisher's exact test.</p><p>Clinical EAE in actively immunized CCRL2 KO mice treated with α-NETA<sup><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112925#nt122\" target=\"_blank\">a</a></sup>.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256044, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.t006", "stats"=>{"downloads"=>2, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_EAE_in_actively_immunized_CCRL2_KO_mice_treated_with_NETA_a_/1256044", "title"=>"Clinical EAE in actively immunized CCRL2 KO mice treated with α-NETA<sup>a</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811804"], "description"=>"a<p>Data are pooled from three independent experiments with each experiment consisting of 7–10 mice per group.</p><p>*p<0.05, as determined by Fisher's exact test;</p><p>***p<0.001, as determined by Mann-Whitney <i>U</i> test.</p>b<p>Determined only for animals that developed EAE.</p><p>Clinical EAE in actively immunized mice treated with α-NETA<sup><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112925#nt113\" target=\"_blank\">a</a></sup>.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256041, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.t003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_EAE_in_actively_immunized_mice_treated_with_NETA_a_/1256041", "title"=>"Clinical EAE in actively immunized mice treated with α-NETA<sup>a</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811789"], "description"=>"<p>(A) Chemerin triggered the association of β-arrestin2 with CMKLR1 in a concentration-dependent manner, as measured by enzymatic complementation assay and quantified by chemiluminescence. For each point the mean ± SEM of n = 9 independent experiments is shown. (B) α-NETA was tested for potency in inhibiting chemerin-mediated β-arrestin2 association with CMKLR1. CMKLR1/β-ARR2 CHO cells were incubated with the indicated concentrations of α-NETA and 7 nM recombinant chemerin (background signal was evaluated in the absence of α-NETA and chemerin). α-NETA was tested for selectivity by evaluating inhibition of chemerin-mediated β-arrestin2 association with GPR1 or CXCL12-mediated β-arrestin2 association with CXCR7. For each point the mean ± SEM of n = 18-19 independent experiments is shown for CMKLR1 and CXCR7, and the mean ± SEM of triplicate wells for one experiment is shown for GPR1. (C) α-NETA was tested for potency and selectivity in inhibiting chemerin-mediated CMKLR1+ cell migration. CMKLR1+ L1.2 cells, CCR9+ MOLT4 cells, CXCR4+ U937 cells, and CXCR5+ NC-37 cells were incubated with the indicated concentrations of α-NETA and then tested for transwell migration to their cognate attractant ligands (7 nM chemerin, 250 nM CCL25, 100 nM CXCL12, 150 nM CXCL13, respectively). Chemotaxis for each cell type was normalized to its maximum migration signal, and cell migration at each concentration of α-NETA was compared with vehicle (0.1% DMSO) for inhibition. For each point the mean ± SEM of 3–5 wells from n = 1–3 independent experiments is shown. *p<0.05 by Student's t-test.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256026, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.g001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_945_NETA_selectively_inhibits_chemerin_stimulated_CMKLR1_association_with_946_arrestin2_/1256026", "title"=>"α-NETA selectively inhibits chemerin-stimulated CMKLR1 association with β-arrestin2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811802"], "description"=>"a<p>PubChem BioAssay identifier.</p>b<p>PubChem, 2014b.</p>c<p>PubChem, 2014a.</p>d<p>Partial effect; 46-58% maximum inhibition at up to 57 µM.</p>e<p>This study.</p>f<p>Agonist activity, EC<sub>50</sub> (µM).</p>g<p>Sastry et al., 1988a.</p>h<p>Single dose (25 µM) tested, 106% inhibition.</p>i<p>Tested up to 92 µM.</p>j<p>Tested up to 57 µM.</p>k<p>Tested up to 35 µM.</p><p>α-NETA target selectivity.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256039, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.t001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_945_NETA_target_selectivity_/1256039", "title"=>"α-NETA target selectivity.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811803"], "description"=>"a<p>IC<sub>50</sub> (µM), mean±SEM, n = 3-14 independent experiments per assay per compound.</p><p>Structure-activity relationship: charged ethyltrimethylamine critical for target potency.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256040, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.t002", "stats"=>{"downloads"=>1, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structure_activity_relationship_charged_ethyltrimethylamine_critical_for_target_potency_/1256040", "title"=>"Structure-activity relationship: charged ethyltrimethylamine critical for target potency.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811801"], "description"=>"<p>(A) EAE was induced in CCRL2 KO mice by active immunization with MOG<sub>35-55</sub>/CFA. Mice received α-NETA (10 mg/kg daily, s.c. injection) beginning at the time of disease induction and were monitored daily for clinical disease. Control mice received either captisol vehicle or no treatment. The pooled data from two independent experiments with 5–6 mice per group is displayed, mean clinical score ± SEM. * <i>p</i><0.05 by Mann-Whitney <i>U</i> test.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256038, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.g006", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_945_NETA_suppresses_clinical_EAE_in_CCRL2_KO_mice_/1256038", "title"=>"α-NETA suppresses clinical EAE in CCRL2 KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811797"], "description"=>"<p>MOG<sub>35–55</sub>/CFA-immunized mice received α-NETA or captisol vehicle once daily. Ten days after immunization, spleen cells and draining LN cells were harvested and re-stimulated <i>in vitro</i> with the indicated concentrations of MOG<sub>35–55</sub>. After 72 h of stimulation, (A) proliferation and (B) cytokine production by spleen cells (<i>left panel</i>) or LN cells (<i>right panel</i>) were evaluated. Proliferation data are presented as mean cpm ± SEM (triplicate wells); ELISA data are presented as mean cytokine concentration ± SEM (triplicate wells). (C) EAE was induced in C57BL/6 mice by passive transfer of MOG<sub>35–55</sub>-reactive lymphocytes derived from vehicle-treated (n = 4) or α-NETA-treated mice (n = 7) as described in the <i>Materials and Methods</i>. The pooled data from two independent experiments is displayed, mean clinical score + SEM.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256034, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.g005", "stats"=>{"downloads"=>5, "page_views"=>84, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Recall_proliferation_and_cytokine_responses_of_lymphocytes_from_945_NETA_treated_mice_and_induction_of_EAE_by_adoptive_transfer_of_MOG_reactive_lymphocytes_/1256034", "title"=>"Recall proliferation and cytokine responses of lymphocytes from α-NETA-treated mice and induction of EAE by adoptive transfer of MOG-reactive lymphocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811792"], "description"=>"<p>(A) C57BL/6 mice were injected s.c. with α-NETA (10 mg/kg) or vehicle daily for 16 days. The mice were then euthanized and vital organs weighed. Each symbol represents an individual mouse, and the bars indicate mean ± SEM, n = 3 mice per group. (B) EAE was induced in C57BL/6 mice by active immunization with MOG<sub>35-55</sub>/CFA. Mice received α-NETA (10 mg/kg daily, s.c. injection) beginning at the time of disease induction and were monitored daily for clinical disease as described in <i>Materials and Methods</i>. Control mice received either captisol vehicle or no treatment. The pooled data from five independent experiments with 7–10 mice per group is displayed, mean clinical score ± SEM. For days 1–15, n = 52 mice per group; for days 16–27, n = 24–25 mice per group. * <i>p</i><0.05 by Mann-Whitney <i>U</i> test. (C) EAE was induced in C57BL/6 mice by passive transfer of MOG<sub>35–55</sub>-reactive lymphocytes derived from actively immunized EAE mice. Recipient mice received either vehicle or α-NETA (10 mg/kg) by daily s.c. injection beginning at the time of transfer and were scored daily for clinical disease. The pooled data from three independent experiments with 3–5 mice per group is displayed, mean clinical score ± SEM. * <i>p</i><0.05 by Mann-Whitney <i>U</i> test.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256029, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.g003", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_945_NETA_is_safe_and_suppresses_clinical_EAE_/1256029", "title"=>"α-NETA is safe and suppresses clinical EAE.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811806"], "description"=>"a<p>On day 16 post-EAE induction, spleen cells were harvested, stained, and analyzed by flow cytometry. n = 5 mice per group.</p><p>*p<0.05, as determined by Student's <i>t</i> test.</p><p>α-NETA limits accumulation of NK cells in the spleen during EAE<sup><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112925#nt120\" target=\"_blank\">a</a></sup>.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256043, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.t005", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NETA_limits_accumulation_of_NK_cells_in_the_spleen_during_EAE_a_/1256043", "title"=>"α-NETA limits accumulation of NK cells in the spleen during EAE<sup>a</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811791"], "description"=>"<p>α-NETA was spiked into 10% captisol (A) or mouse plasma (B) and incubated at the indicated temperatures. At the indicated times, the samples were quenched and analyzed by mass spectrometry. The stability of Benfluorex (positive control compound) was also determined (B). Mean ± SD of triplicate wells for each point is displayed.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256028, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.g002", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_945_NETA_stability_/1256028", "title"=>"α-NETA stability.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-01 03:34:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1811805"], "description"=>"a<p>Data are pooled from three independent experiments with each experiment consisting of 3–5 mice per group.</p><p>*p<0.05, as determined by Mann-Whitney <i>U</i> test.</p>b<p>Determined only for animals that developed EAE.</p><p>Clinical EAE in adoptive transfer model treated with α-NETA<sup><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112925#nt117\" target=\"_blank\">a</a></sup>.</p>", "links"=>[], "tags"=>["CMKLR 1 KO", "Novel CMKLR 1", "animal model", "histological EAE", "CMKLR 1", "encephalitogenic T cells", "disease activity", "chemoattractant receptor", "ms", "molecule antagonist", "target leukocyte trafficking pathways", "Disease Therapies", "CMKLR 1 KO phenotype", "CMKLR 1 inhibitors", "histological features", "killer cells", "cell infiltrates", "C 57BL mice", "Molecule Antagonist Suppresses CNS Autoimmune", "effector cells", "NETA", "Dendritic cells"], "article_id"=>1256042, "categories"=>["Biological Sciences"], "users"=>["Kareem L. Graham", "Jian V. Zhang", "Susanna Lewén", "Thomas M. Burke", "Ton Dang", "Maria Zoudilova", "Raymond A. Sobel", "Eugene C. Butcher", "Brian A. Zabel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112925.t004", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_EAE_in_adoptive_transfer_model_treated_with_NETA_a_/1256042", "title"=>"Clinical EAE in adoptive transfer model treated with α-NETA<sup>a</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-01 03:34:43"}

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