AIM2 Drives Joint Inflammation in a Self-DNA Triggered Model of Chronic Polyarthritis
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{"title"=>"AIM2 drives joint inflammation in a self-DNA triggered model of chronic polyarthritis", "type"=>"journal", "authors"=>[{"first_name"=>"Christopher", "last_name"=>"Jakobs", "scopus_author_id"=>"55540821700"}, {"first_name"=>"Sven", "last_name"=>"Perner", "scopus_author_id"=>"14024703800"}, {"first_name"=>"Veit", "last_name"=>"Hornung", "scopus_author_id"=>"6603665800"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84938515167", "pui"=>"605407818", "doi"=>"10.1371/journal.pone.0131702", "sgr"=>"84938515167", "pmid"=>"26114879"}, "id"=>"c7575d38-638e-3792-8589-28acfc523383", "abstract"=>"Mice lacking DNase II display a polyarthritis-like disease phenotype that is driven by translocation of self-DNA into the cytoplasm of phagocytic cells, where it is sensed by pattern recognition receptors. While pro-inflammatory gene expression is non-redundantly ...", "link"=>"http://www.mendeley.com/research/aim2-drives-joint-inflammation-selfdna-triggered-model-chronic-polyarthritis", "reader_count"=>21, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>2, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"France"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2152998"], "description"=>"<p><b>A:</b> Serum was collected from <i>Aim2</i><sup><i>+/+</i></sup><i>Dnase2</i><sup><i>-/-</i></sup><i>Ifnar1</i><sup><i>-/-</i></sup>, <i>Aim2</i><sup><i>-/-</i></sup><i>Dnase2</i><sup><i>-/-</i></sup><i>Ifnar1</i><sup><i>-/-</i></sup>, <i>Aim2</i><sup><i>+/+</i></sup><i>Dnase2</i><sup><i>+/+</i></sup><i>Ifnar1</i><sup><i>-/-</i></sup><i>and Aim2</i><sup><i>-/-</i></sup><i>Dnase2</i><sup><i>+/+</i></sup><i>Ifnar1</i><sup><i>-/-</i></sup> mice at the age of 15 month and analyzed for the depicted cytokines. <b>B:</b> Spleen weight and representative pictures of spleens from mice at the age of 15 month. <b>C:</b> Relative IFNβ gene expression in spleen tissue normalized to the expression level of HPRT1 is shown. <b>D:</b> Anti-cyclic citrullinated peptide antibody (Anti-CCP-AB) was measured in serum samples as in (<b>A</b>). Data are presented as mean values + SEM, whereas statistical significance was assessed using a two-tailed, unpaired t-test comparing the <i>Dnase2</i><sup><i>-/-</i></sup> cohorts.</p>", "links"=>[], "tags"=>["disease model", "DNase II display", "AIM 2.", "histopathological findings", "DNA species", "sting", "phagocytic cells", "role", "Chronic Polyarthritis Mice", "inflammation", "aim 2 Drives Joint Inflammation", "DNase II", "Pattern recognition receptors", "AIM 2", "AIM 2 inflammasome", "inflammasome pathway"], "article_id"=>1466264, "categories"=>["Uncategorised"], "users"=>["Christopher Jakobs", "Sven Perner", "Veit Hornung"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131702.g002", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Systemic_proinflammatory_status_in_Dnase2__mice_is_independent_of_AIM2_/1466264", "title"=>"Systemic proinflammatory status in <i>Dnase2</i><sup><i>-/-</i></sup> mice is independent of AIM2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-26 04:28:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/2152999"], "description"=>"<p><b>A:</b> Protein lysates were generated from the joints of 15 months old mice and immunoblotted for the presence of cleaved Caspase-1, whereas β-Actin served as a loading control. Three independent protein lysates were analyzed per cohort. <b>B:</b> Cytokine levels of lysates as in (<b>A</b>) were determined. <b>C</b> and <b>D:</b> qPCR analysis of joints of the four different cohorts is shown for the indicated transcripts. The mRNA levels for the indicated cytokines are expressed relative to mRNA of HPRT1. Data are presented as mean values + SEM, whereas statistical significance was assessed using a two-tailed, unpaired t-test comparing the <i>Dnase2</i><sup><i>-/-</i></sup> cohorts.</p>", "links"=>[], "tags"=>["disease model", "DNase II display", "AIM 2.", "histopathological findings", "DNA species", "sting", "phagocytic cells", "role", "Chronic Polyarthritis Mice", "inflammation", "aim 2 Drives Joint Inflammation", "DNase II", "Pattern recognition receptors", "AIM 2", "AIM 2 inflammasome", "inflammasome pathway"], "article_id"=>1466265, "categories"=>["Uncategorised"], "users"=>["Christopher Jakobs", "Sven Perner", "Veit Hornung"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131702.g003", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_expression_of_proinflammatory_cytokines_in_joints_of_Dnase2_deficient_mice_relies_on_AIM2_/1466265", "title"=>"Gene expression of proinflammatory cytokines in joints of Dnase2 deficient mice relies on AIM2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-26 04:28:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153000"], "description"=>"<p><b>A:</b> Joint sections of 15 month old mice of the depicted genotypes were stained with haematoxylin/eosin, F4/80 and MMP3. B, Bone; BM, Bone marrow; C, cartilage; I, Infiltrate; S, Synovitis. <b>B:</b> Histological scores of joint sections from 15 month old mice stained with HE, F4/80 or MMP3: 0, no overt signs of synovitis / infiltration; 1, low grade synovitis / infiltration; 2, intermediate grade synovitis / infiltration; 3, high grade synovitis / infiltration. <b>C:</b> RNAs were isolated from the joints of 15 months old mice to quantify MMP3 expression normalized to HPRT1. Data are presented as mean values + SEM, whereas statistical significance was assessed using a two-tailed, unpaired t-test comparing the <i>Dnase2</i><sup><i>-/-</i></sup> cohorts. <b>D</b>: Protein lysates were generated from the joints of 15 months old mice and immunoblotted for the presence of MMP3, whereas β-Actin served as a loading control. Three independent protein lysates were analyzed per cohort. Data are presented as mean values + SEM, whereas statistical significance was assessed using a two-tailed Mann-Whitney test (<b>b</b>) or using a two-tailed, unpaired t-test (<b>c</b>) comparing the <i>Dnase2</i><sup><i>-/-</i></sup> cohorts.</p>", "links"=>[], "tags"=>["disease model", "DNase II display", "AIM 2.", "histopathological findings", "DNA species", "sting", "phagocytic cells", "role", "Chronic Polyarthritis Mice", "inflammation", "aim 2 Drives Joint Inflammation", "DNase II", "Pattern recognition receptors", "AIM 2", "AIM 2 inflammasome", "inflammasome pathway"], "article_id"=>1466266, "categories"=>["Uncategorised"], "users"=>["Christopher Jakobs", "Sven Perner", "Veit Hornung"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131702.g004", "stats"=>{"downloads"=>2, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Local_inflammation_of_joints_in_Dnase2_deficient_mice_is_largely_AIM2_dependent_/1466266", "title"=>"Local inflammation of joints in Dnase2 deficient mice is largely AIM2 dependent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-26 04:28:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153001", "https://ndownloader.figshare.com/files/2153002"], "description"=>"<div><p>Mice lacking DNase II display a polyarthritis-like disease phenotype that is driven by translocation of self-DNA into the cytoplasm of phagocytic cells, where it is sensed by pattern recognition receptors. While pro-inflammatory gene expression is non-redundantly linked to the presence of STING in these mice, the contribution of the inflammasome pathway has not been explored. To this end, we studied the role of the DNA-sensing inflammasome receptor AIM2 in this self-DNA driven disease model. Arthritis-prone mice lacking AIM2 displayed strongly decreased signs of joint inflammation and associated histopathological findings. This was paralleled with a reduction of caspase-1 activation and pro-inflammatory cytokine production in diseased joints. Interestingly, systemic signs of inflammation that are associated with the lack of DNase II were not dependent on AIM2. Taken together, these data suggest a tissue-specific role for the AIM2 inflammasome as a sensor for endogenous DNA species in the course of a ligand-dependent autoinflammatory condition.</p></div>", "links"=>[], "tags"=>["disease model", "DNase II display", "AIM 2.", "histopathological findings", "DNA species", "sting", "phagocytic cells", "role", "Chronic Polyarthritis Mice", "inflammation", "aim 2 Drives Joint Inflammation", "DNase II", "Pattern recognition receptors", "AIM 2", "AIM 2 inflammasome", "inflammasome pathway"], "article_id"=>1466267, "categories"=>["Uncategorised"], "users"=>["Christopher Jakobs", "Sven Perner", "Veit Hornung"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0131702.s001", "https://dx.doi.org/10.1371/journal.pone.0131702.s002"], "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AIM2_Drives_Joint_Inflammation_in_a_Self_DNA_Triggered_Model_of_Chronic_Polyarthritis_/1466267", "title"=>"AIM2 Drives Joint Inflammation in a Self-DNA Triggered Model of Chronic Polyarthritis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-06-26 04:28:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/2152997"], "description"=>"<p><b>A:</b><i>Aim2</i><sup><i>+/+</i></sup><i>Dnase2</i><sup><i>-/-</i></sup><i>Ifnar1</i><sup><i>-/-</i></sup>, <i>Aim2</i><sup><i>-/-</i></sup><i>Dnase2</i><sup><i>-/-</i></sup><i>Ifnar1</i><sup><i>-/-</i></sup>, <i>Aim2</i><sup><i>+/+</i></sup><i>Dnase2</i><sup><i>+/+</i></sup><i>Ifnar1</i><sup><i>-/-</i></sup><i>and Aim2</i><sup><i>-/-</i></sup><i>Dnase2</i><sup><i>+/+</i></sup><i>Ifnar1</i><sup><i>-/-</i></sup> mice were scored for joint swelling at indicated time points in a blinded fashion. Statistical significance was assessed using a two-tailed Mann-Whitney test comparing Dnase2<sup><i>-/-</i></sup> cohorts at 8, 12 or 15 months. <b>B:</b> Representative pictures of fore-and hind pads of Aim2<sup><i>+/+</i></sup> Dnase2<sup><i>-/-</i></sup> Ifnar1<sup><i>-/-</i></sup>, Aim2<sup><i>-/-</i></sup> Dnase2<sup><i>-/-</i></sup> Ifnar1<sup><i>-/-</i></sup>, Aim2<sup><i>+/+</i></sup> Dnase2<sup><i>+/+</i></sup> Ifnar1<sup><i>-/-</i></sup> and Aim2<sup><i>-/-</i></sup> Dnase2<sup><i>+/+</i></sup> Ifnar1<sup><i>-/-</i></sup> mice at the age of 15 month are shown.</p>", "links"=>[], "tags"=>["disease model", "DNase II display", "AIM 2.", "histopathological findings", "DNA species", "sting", "phagocytic cells", "role", "Chronic Polyarthritis Mice", "inflammation", "aim 2 Drives Joint Inflammation", "DNase II", "Pattern recognition receptors", "AIM 2", "AIM 2 inflammasome", "inflammasome pathway"], "article_id"=>1466263, "categories"=>["Uncategorised"], "users"=>["Christopher Jakobs", "Sven Perner", "Veit Hornung"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131702.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Swelling_of_joints_in_the_context_of_Dnase2_deficiency_is_AIM2_dependent_/1466263", "title"=>"Swelling of joints in the context of <i>Dnase2</i>-deficiency is AIM2-dependent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-26 04:28:08"}

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