Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology
Publication Date
January 14, 2016
Journal
PLOS Pathogens
Authors
Marcela Montes De Oca, Rajiv Kumar, Fabian De Labastida Rivera, Fiona H Amante, et al
Volume
12
Issue
1
Pages
e1005398
DOI
https://dx.plos.org/10.1371/journal.ppat.1005398
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005398
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/26765224
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713066
Europe PMC
http://europepmc.org/abstract/MED/26765224
Web of Science
000369374500044
Scopus
84956808926
Mendeley
http://www.mendeley.com/research/blimp1dependent-il10-production-tr1-cells-regulates-tnfmediated-tissue-pathology
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology", "type"=>"journal", "authors"=>[{"first_name"=>"Marcela", "last_name"=>"Montes de Oca", "scopus_author_id"=>"57091377600"}, {"first_name"=>"Rajiv", "last_name"=>"Kumar", "scopus_author_id"=>"55492126700"}, {"first_name"=>"Fabian", "last_name"=>"de Labastida Rivera", "scopus_author_id"=>"36131392100"}, {"first_name"=>"Fiona H.", "last_name"=>"Amante", "scopus_author_id"=>"6508336120"}, {"first_name"=>"Meru", "last_name"=>"Sheel", "scopus_author_id"=>"24468986900"}, {"first_name"=>"Rebecca J.", "last_name"=>"Faleiro", "scopus_author_id"=>"55945082300"}, {"first_name"=>"Patrick T.", "last_name"=>"Bunn", "scopus_author_id"=>"54402417400"}, {"first_name"=>"Shannon E.", "last_name"=>"Best", "scopus_author_id"=>"37096720200"}, {"first_name"=>"Lynette", "last_name"=>"Beattie", "scopus_author_id"=>"6603858358"}, {"first_name"=>"Susanna S.", "last_name"=>"Ng", "scopus_author_id"=>"56449880300"}, {"first_name"=>"Chelsea L.", "last_name"=>"Edwards", "scopus_author_id"=>"56199332500"}, {"first_name"=>"Werner", "last_name"=>"Muller", "scopus_author_id"=>"55251783500"}, {"first_name"=>"Erika", "last_name"=>"Cretney", "scopus_author_id"=>"6602972932"}, {"first_name"=>"Stephen L.", "last_name"=>"Nutt", "scopus_author_id"=>"7004301216"}, {"first_name"=>"Mark J.", "last_name"=>"Smyth", "scopus_author_id"=>"7202702094"}, {"first_name"=>"Ashraful", "last_name"=>"Haque", "scopus_author_id"=>"9734348600"}, {"first_name"=>"Geoffrey R.", "last_name"=>"Hill", "scopus_author_id"=>"55586304200"}, {"first_name"=>"Shyam", "last_name"=>"Sundar", "scopus_author_id"=>"56819423800"}, {"first_name"=>"Axel", "last_name"=>"Kallies", "scopus_author_id"=>"6603640059"}, {"first_name"=>"Christian R.", "last_name"=>"Engwerda", "scopus_author_id"=>"6701380722"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "scopus"=>"2-s2.0-84956808926", "sgr"=>"84956808926", "pui"=>"608034568", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)", "pmid"=>"26765224", "doi"=>"10.1371/journal.ppat.1005398"}, "id"=>"bcae8601-2bd5-3279-8854-1780bf5bf239", "abstract"=>"Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation.", "link"=>"http://www.mendeley.com/research/blimp1dependent-il10-production-tr1-cells-regulates-tnfmediated-tissue-pathology", "reader_count"=>29, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Librarian"=>3, "Researcher"=>5, "Student > Ph. D. Student"=>11, "Student > Master"=>2, "Student > Bachelor"=>5, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Librarian"=>3, "Researcher"=>5, "Student > Ph. D. Student"=>11, "Student > Master"=>2, "Student > Bachelor"=>5, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>4, "Computer Science"=>2, "Immunology and Microbiology"=>9}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>9}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Japan"=>1}, "group_count"=>1}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84956808926"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84956808926?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84956808926&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84956808926&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84956808926", "dc:identifier"=>"SCOPUS_ID:84956808926", "eid"=>"2-s2.0-84956808926", "dc:title"=>"Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology", "dc:creator"=>"Montes de Oca M.", "prism:publicationName"=>"PLoS Pathogens", "prism:issn"=>"15537366", "prism:eIssn"=>"15537374", "prism:volume"=>"12", "prism:issueIdentifier"=>"1", "prism:pageRange"=>nil, "prism:coverDate"=>"2016-01-01", "prism:coverDisplayDate"=>"2016", "prism:doi"=>"10.1371/journal.ppat.1005398", "citedby-count"=>"33", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"University of Queensland", "affiliation-city"=>"Brisbane", "affiliation-country"=>"Australia"}, {"@_fa"=>"true", "affilname"=>"QIMR Berghofer Medical Research Institute", "affiliation-city"=>"Brisbane", "affiliation-country"=>"Australia"}], "pubmed-id"=>"26765224", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e1005398", "source-id"=>"4000151809", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplospathogens%2Farticle%3Fid%3D10.1371%252Fjournal.ppat.1005398", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"103", "xml_views"=>"2", "html_views"=>"1164"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"55", "xml_views"=>"2", "html_views"=>"345"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"121"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"188"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"24", "xml_views"=>"0", "html_views"=>"300"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"162"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"25", "xml_views"=>"0", "html_views"=>"97"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"29", "xml_views"=>"0", "html_views"=>"181"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"86"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"103"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"95"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"1", "html_views"=>"70"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"64"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"24", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"15", "xml_views"=>"2", "html_views"=>"64"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"18", "xml_views"=>"1", "html_views"=>"75"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"47"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"37", "xml_views"=>"0", "html_views"=>"67"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"54"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"47"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"52"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"16", "xml_views"=>"3", "html_views"=>"24"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"24"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"40"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"20", "xml_views"=>"1", "html_views"=>"30"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"17"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"10"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2627613"], "description"=>"<p><b>(A)</b><i>Prdm1</i><sup>fl/fl</sup> and <i>Prdm1</i><sup>ΔT</sup> C57BL/6 mice were infected with PcAS and peripheral parasitemia was measured beginning at day 4 post infection (p.i.). (<b>B)</b> Splenic CD4<sup>+</sup> T cell responses were assessed by flow cytometry, as indicated, at day 15 p.i.. The frequency and number of activated CD4<sup>+</sup> T cells (CD11a<sup>+</sup>CD49d<sup>+</sup>) (<b>C)</b>, Th1 cells (IFNγ<sup>+</sup>Tbet<sup>+</sup>) (<b>D)</b> and Tr1 cells (IFNγ<sup>+</sup>IL-10<sup>+</sup>) (<b>E)</b> were measured. Representative of 3 independent experiments, mean ±SEM, n = 5 in each group in each experiment, **p<0.01, *p<0.05, Mann-Whitney U test.</p>", "links"=>[], "tags"=>["ifn", "TNF regulation", "inflammation", "vl", "blimp", "il", "Tr 1 cells", "Tr 1 cell development"], "article_id"=>1637653, "categories"=>["Biological Sciences"], "users"=>["Marcela Montes de Oca", "Rajiv Kumar", "Fabian de Labastida Rivera", "Fiona H Amante", "Meru Sheel", "Rebecca J. Faleiro", "Patrick T. Bunn", "Shannon E. Best", "Lynette Beattie", "Susanna S. Ng", "Chelsea L. Edwards", "Werner Müller", "Erika Cretney", "Stephen L. Nutt", "Mark J. Smyth", "Ashraful Haque", "Geoffrey R. Hill", "Shyam Sundar", "Axel Kallies", "Christian R. Engwerda"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005398.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blimp_1_inhibits_the_control_of_parasite_growth_during_experimental_malaria_/1637653", "title"=>"Blimp-1 inhibits the control of parasite growth during experimental malaria.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:36:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627614"], "description"=>"<p><b>(A)</b><i>Prdm1</i><sup><i>GFP/+</i></sup> (black-filled histograms) and WT (grey-filled histograms) mice were infected with PcAS. Blimp-1/GFP expression measured on CD4<sup>+</sup> T cells producing IL-10, IFNγ and TNF at day 15 p.i.. (<b>B)</b> Kinetics of Blimp-1/GFP expression measured in various cytokine producing CD4<sup>+</sup> T cells, as indicated, beginning at day 5 p.i.. <b>(C)</b><i>Prdm1</i><sup><i>GFP/+</i></sup> and WT mice were infected with <i>L</i>. <i>donovani</i> and the kinetics of Blimp-1 expression measured in the spleen and liver. (<b>D)</b> FACS plots showing gated CD4<sup>+</sup> T cell IL-10 and IFNγ production from <i>Prdm1</i><sup><i>GFP/+</i></sup> mice treated with 500 μg of polyclonal rat IgG (black bars in (<b>E</b>)) or anti-IL-12 (C17.8; white bars in (<b>E</b>)), as indicated, prior to infection and every 3 days following infection until day 14 p.i.. (<b>E</b>) The frequencies of IL-10 and IFNγ-producing CD4<sup>+</sup> and CD8<sup>+</sup> T cells, as well as Blimp-1 expressing CD4<sup>+</sup> and CD8<sup>+</sup> T cells, were determined by flow cytometry at day 14 p.i.. Representative of 3 similar experiments, mean ±SEM, n = 5 in each group in each experiment, **p<0.01, Mann-Whitney U test.</p>", "links"=>[], "tags"=>["ifn", "TNF regulation", "inflammation", "vl", "blimp", "il", "Tr 1 cells", "Tr 1 cell development"], "article_id"=>1637654, "categories"=>["Biological Sciences"], "users"=>["Marcela Montes de Oca", "Rajiv Kumar", "Fabian de Labastida Rivera", "Fiona H Amante", "Meru Sheel", "Rebecca J. Faleiro", "Patrick T. Bunn", "Shannon E. Best", "Lynette Beattie", "Susanna S. Ng", "Chelsea L. Edwards", "Werner Müller", "Erika Cretney", "Stephen L. Nutt", "Mark J. Smyth", "Ashraful Haque", "Geoffrey R. Hill", "Shyam Sundar", "Axel Kallies", "Christian R. Engwerda"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005398.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blimp_1_controls_CD4_T_cell_derived_IL_10_production_/1637654", "title"=>"Blimp-1 controls CD4<sup>+</sup> T cell derived IL-10 production.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:36:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627615"], "description"=>"<p><b>(A)</b><i>PRDM1</i> and (<b>B</b>) IL-10 mRNA accumulation in purified CD4<sup>+</sup> cells isolated from the PBMCs, as well as (<b>C</b>) plasma IL-10 levels from VL patients before (closed circles; Pre) and 28 days after (open circles; Post) drug treatment. Data are from the same 10 paired samples, **p<0.01, *p<0.05, Wilcoxon signed-rank test.</p>", "links"=>[], "tags"=>["ifn", "TNF regulation", "inflammation", "vl", "blimp", "il", "Tr 1 cells", "Tr 1 cell development"], "article_id"=>1637655, "categories"=>["Biological Sciences"], "users"=>["Marcela Montes de Oca", "Rajiv Kumar", "Fabian de Labastida Rivera", "Fiona H Amante", "Meru Sheel", "Rebecca J. Faleiro", "Patrick T. Bunn", "Shannon E. Best", "Lynette Beattie", "Susanna S. Ng", "Chelsea L. Edwards", "Werner Müller", "Erika Cretney", "Stephen L. Nutt", "Mark J. Smyth", "Ashraful Haque", "Geoffrey R. Hill", "Shyam Sundar", "Axel Kallies", "Christian R. Engwerda"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005398.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Elevated_Blimp_1_levels_in_CD4_T_cells_from_VL_patients_were_associated_with_increased_IL_10_production_/1637655", "title"=>"Elevated Blimp-1 levels in CD4<sup>+</sup> T cells from VL patients were associated with increased IL-10 production.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:36:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627616"], "description"=>"<p><i>Prdm1</i><sup>fl/fl</sup> and <i>Prdm1</i><sup>ΔT</sup> C57BL/6 mice were infected with <i>L</i>. <i>donovani</i> and spleen (<b>A</b>) and liver (<b>D</b>) parasite burdens were measured at times indicated. The frequency of Th1 and Tr1 cells in the spleen (<b>B</b>) and liver (<b>E)</b> were measured by flow cytometry. Organ weights and frequencies of TNF producing CD4<sup>+</sup> T cells in the spleen (<b>C</b>) and liver (<b>F)</b> were also assessed, as were serum TNF and IFNγ levels (<b>G</b>). Antigen-specific Th1 cell frequency (<b>H</b>), IFNγ, TNF and IL-10 production (<b>I</b>) were measured in splenocytes after 24 hours of culture in the presence of parasite antigen at times indicated. In all panels, closed shapes represent <i>Prdm1</i><sup>fl/fl</sup> mice, while open shapes indicate <i>Prdm1</i><sup>ΔT</sup> littermates. Representative of 5 similar experiments, mean ±SEM, n = 5–6 in each group in each experiment, **p<0.01, *p<0.05, Mann-Whitney U test.</p>", "links"=>[], "tags"=>["ifn", "TNF regulation", "inflammation", "vl", "blimp", "il", "Tr 1 cells", "Tr 1 cell development"], "article_id"=>1637656, "categories"=>["Biological Sciences"], "users"=>["Marcela Montes de Oca", "Rajiv Kumar", "Fabian de Labastida Rivera", "Fiona H Amante", "Meru Sheel", "Rebecca J. Faleiro", "Patrick T. Bunn", "Shannon E. Best", "Lynette Beattie", "Susanna S. Ng", "Chelsea L. Edwards", "Werner Müller", "Erika Cretney", "Stephen L. Nutt", "Mark J. Smyth", "Ashraful Haque", "Geoffrey R. Hill", "Shyam Sundar", "Axel Kallies", "Christian R. Engwerda"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005398.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blimp_1_inhibits_the_control_of_parasite_growth_during_experimental_visceral_leishmaniasis_/1637656", "title"=>"Blimp-1 inhibits the control of parasite growth during experimental visceral leishmaniasis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:36:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627617"], "description"=>"<p><i>Prdm1</i><sup>fl/fl</sup> and <i>Prdm1</i><sup>ΔTreg</sup> C57BL/6 mice were infected with <i>L</i>.<i>donovani</i>. Spleen and liver weights (<b>A</b>), parasite burdens (<b>B</b>), frequency of Th1 (<b>C</b>) and Tr1 (<b>D</b>) cells, as well as serum TNF and IFNγ levels (<b>E</b>) were measured at day 28 p.i.. Experiment performed once, mean ±SEM, n = 5, *p<0.05, Mann-Whitney U test.</p>", "links"=>[], "tags"=>["ifn", "TNF regulation", "inflammation", "vl", "blimp", "il", "Tr 1 cells", "Tr 1 cell development"], "article_id"=>1637657, "categories"=>["Uncategorised"], "users"=>["Marcela Montes de Oca", "Rajiv Kumar", "Fabian de Labastida Rivera", "Fiona H Amante", "Meru Sheel", "Rebecca J. Faleiro", "Patrick T. Bunn", "Shannon E. Best", "Lynette Beattie", "Susanna S. Ng", "Chelsea L. Edwards", "Werner Müller", "Erika Cretney", "Stephen L. Nutt", "Mark J. Smyth", "Ashraful Haque", "Geoffrey R. Hill", "Shyam Sundar", "Axel Kallies", "Christian R. Engwerda"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005398.g005", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blimp_1_expression_by_Treg_cells_has_little_influence_over_host_immune_responses_and_parasite_growth_during_experimental_visceral_leishmaniasis_/1637657", "title"=>"Blimp-1 expression by Treg cells has little influence over host immune responses and parasite growth during experimental visceral leishmaniasis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:36:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627618"], "description"=>"<p><i>Prdm1</i><sup>fl/fl</sup>, <i>Il-10</i><sup><i>fl/fl</i></sup>, <i>Prdm1</i><sup><i>ΔT</i></sup> and <i>Il-10</i><sup><i>ΔT</i></sup> C57BL/6 mice were infected with <i>L</i>. <i>donovani</i>. Spleen parasite burdens were determined (<b>A</b>) and organ weights were measured (<b>B</b>) at day 14 p.i. The number of MZMs per mm<sup>2</sup> of spleen tissue was determined (<b>C</b>), as described in the Materials and Methods. Representative images showing nucleated cells (blue; DAPI) and MZM (indicated by uptake of FITC-dextran, green) (<b>C</b>) (objective 20x, scale bars 500 μm). <i>Il-10r</i><sup><i>fl/fl</i></sup> and <i>Il-10r</i><sup><i>ΔM</i></sup> C57BL/6 mice were infected with <i>L</i>. <i>donovani</i> and spleen parasite burdens (<b>D</b>) and spleen weights were measured (<b>E</b>) at day 14 p.i., as was serum TNF and IFNγ levels (<b>F</b>). The number of MZMs per mm<sup>2</sup> of spleen tissue was also determined at day 14 p.i. (<b>G</b>). Representative of 3 similar experiments, mean ±SEM, n = 5–7 in each group in each experiment, **p<0.01, *p<0.05, Mann-Whitney U test.</p>", "links"=>[], "tags"=>["ifn", "TNF regulation", "inflammation", "vl", "blimp", "il", "Tr 1 cells", "Tr 1 cell development"], "article_id"=>1637658, "categories"=>["Biological Sciences"], "users"=>["Marcela Montes de Oca", "Rajiv Kumar", "Fabian de Labastida Rivera", "Fiona H Amante", "Meru Sheel", "Rebecca J. Faleiro", "Patrick T. Bunn", "Shannon E. Best", "Lynette Beattie", "Susanna S. Ng", "Chelsea L. Edwards", "Werner Müller", "Erika Cretney", "Stephen L. Nutt", "Mark J. Smyth", "Ashraful Haque", "Geoffrey R. Hill", "Shyam Sundar", "Axel Kallies", "Christian R. Engwerda"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005398.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_10_signaling_to_myeloid_cells_protects_macrophages_from_TNF_mediated_destruction_/1637658", "title"=>"IL-10 signaling to myeloid cells protects macrophages from TNF-mediated destruction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:36:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627624"], "description"=>"<p><i>Prdm1</i><sup>fl/fl</sup> and <i>Prdm1</i><sup>ΔT</sup> C57BL/6 mice were infected with <i>L</i>. <i>donovani</i> and received either TNF blockade (Enbrel) or control human IgG (INTRAGAM), as indicated. Spleen parasite burdens (<b>A</b>) and organ weights (<b>B</b>) were measured at day 14 p.i., as was the number of MZMs per mm<sup>2</sup> of spleen tissue (<b>C</b>), following labelling of spleen tissue sections for nucleated cells (blue; DAPI) and MZM (indicated by uptake of FITC-dextran, green) (<b>D</b>). To examine lymphocyte trafficking, two hours prior to tissue collection, mice were injected with 2 x 10<sup>7</sup> fluorescently labelled splenocytes. Spleen tissue sections were examined (<b>E</b>) for transferred splenocytes (white; left and right panels), T (CD3, blue; right panels) and B (B220, yellow; right panels) cell zones (10x magnification, scale bars = 200 μm). The total number of transferred cells in a given area of spleen tissue, the number of transferred cells per mm<sup>2</sup> of white pulp (WP) area and total area of WP were calculated as described in Material and Methods (<b>F</b>). For each mouse, four fields of view that were identical in size were imaged. Representative of 3 similar experiments, mean ±SEM, n = 5–6 in each group in each experiment, ***p<0.001, **p<0.01, *p<0.05, One-way ANOVA (Kruskal-Wallis test).</p>", "links"=>[], "tags"=>["ifn", "TNF regulation", "inflammation", "vl", "blimp", "il", "Tr 1 cells", "Tr 1 cell development"], "article_id"=>1637660, "categories"=>["Biological Sciences"], "users"=>["Marcela Montes de Oca", "Rajiv Kumar", "Fabian de Labastida Rivera", "Fiona H Amante", "Meru Sheel", "Rebecca J. Faleiro", "Patrick T. Bunn", "Shannon E. Best", "Lynette Beattie", "Susanna S. Ng", "Chelsea L. Edwards", "Werner Müller", "Erika Cretney", "Stephen L. Nutt", "Mark J. Smyth", "Ashraful Haque", "Geoffrey R. Hill", "Shyam Sundar", "Axel Kallies", "Christian R. Engwerda"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005398.g007", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Early_loss_of_marginal_zone_macrophages_and_impaired_lymphocyte_trafficking_is_a_TNF_dependent_process_/1637660", "title"=>"Early loss of marginal zone macrophages and impaired lymphocyte trafficking is a TNF dependent process.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:36:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627630"], "description"=>"<p>C57BL/6 IFNγR<sup>-/-</sup> and WT mice were infected with <i>L</i>.<i>donovani</i>. (<b>A</b>) Representative images of MZMs at day 28 p.i. (objective 20x, scale bars 500 μm; staining as in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005398#ppat.1005398.g004\" target=\"_blank\">Fig 4D</a>). Spleen weights were measured at times indicated (<b>B</b>) and the number of MZMs per mm<sup>2</sup> of spleen tissue was determined at day 28 p.i. (<b>C</b>), as described in the Materials and Methods. Spleen and liver parasite burdens were measured (<b>D</b>) at day 28 p.i. as was serum TNF and IFNγ levels (<b>E</b>) Representative of 3 similar experiments, mean ±SEM, n = 6 in each group in each experiment, **p<0.01, *p<0.05, Mann-Whitney U test.</p>", "links"=>[], "tags"=>["ifn", "TNF regulation", "inflammation", "vl", "blimp", "il", "Tr 1 cells", "Tr 1 cell development"], "article_id"=>1637661, "categories"=>["Uncategorised"], "users"=>["Marcela Montes de Oca", "Rajiv Kumar", "Fabian de Labastida Rivera", "Fiona H Amante", "Meru Sheel", "Rebecca J. Faleiro", "Patrick T. Bunn", "Shannon E. Best", "Lynette Beattie", "Susanna S. Ng", "Chelsea L. Edwards", "Werner Müller", "Erika Cretney", "Stephen L. Nutt", "Mark J. Smyth", "Ashraful Haque", "Geoffrey R. Hill", "Shyam Sundar", "Axel Kallies", "Christian R. Engwerda"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005398.g008", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IFN_947_signalling_drives_TNF_production_and_contributes_to_splenic_pathology_/1637661", "title"=>"IFNγ signalling drives TNF production and contributes to splenic pathology.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:36:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/2627635", "https://ndownloader.figshare.com/files/2627636", "https://ndownloader.figshare.com/files/2627637", "https://ndownloader.figshare.com/files/2627638", "https://ndownloader.figshare.com/files/2627639", "https://ndownloader.figshare.com/files/2627640", "https://ndownloader.figshare.com/files/2627641"], "description"=>"<div><p>Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4<sup>+</sup> T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation.</p></div>", "links"=>[], "tags"=>["ifn", "TNF regulation", "inflammation", "vl", "blimp", "il", "Tr 1 cells", "Tr 1 cell development"], "article_id"=>1637663, "categories"=>["Biological Sciences"], "users"=>["Marcela Montes de Oca", "Rajiv Kumar", "Fabian de Labastida Rivera", "Fiona H Amante", "Meru Sheel", "Rebecca J. Faleiro", "Patrick T. Bunn", "Shannon E. Best", "Lynette Beattie", "Susanna S. Ng", "Chelsea L. Edwards", "Werner Müller", "Erika Cretney", "Stephen L. Nutt", "Mark J. Smyth", "Ashraful Haque", "Geoffrey R. Hill", "Shyam Sundar", "Axel Kallies", "Christian R. Engwerda"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005398.s001", "https://dx.doi.org/10.1371/journal.ppat.1005398.s002", "https://dx.doi.org/10.1371/journal.ppat.1005398.s003", "https://dx.doi.org/10.1371/journal.ppat.1005398.s004", "https://dx.doi.org/10.1371/journal.ppat.1005398.s005", "https://dx.doi.org/10.1371/journal.ppat.1005398.s006", "https://dx.doi.org/10.1371/journal.ppat.1005398.s007"], "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blimp_1_Dependent_IL_10_Production_by_Tr1_Cells_Regulates_TNF_Mediated_Tissue_Pathology_/1637663", "title"=>"Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2016-01-28 12:36:24"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"39", "full-text"=>"39", "pdf"=>"19", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"22", "full-text"=>"25", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"24", "full-text"=>"31", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"31", "full-text"=>"43", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"27", "full-text"=>"27", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"14", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"19", "full-text"=>"18", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"27", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"15", "supp-data"=>"9", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"23", "full-text"=>"24", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"24", "full-text"=>"22", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"20", "full-text"=>"21", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"13", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"27", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
Loading … Spinner
There are currently no alerts