{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:07:09Z","timestamp":1790496429234,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We undertook this study to evaluate the activation and functional relevance of inflammasome pathways in ankylosing spondylitis (AS) patients and rodent models and their relationship to dysbiosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An inflammasome pathway was evaluated in the gut and peripheral blood from 40 AS patients using quantitative reverse transcriptase\u2013polymerase chain reaction (qRT\u2010PCR), immunohistochemistry (IHC), flow cytometry, and confocal microscopy, and was compared to that of 20 healthy controls and 10 patients with Crohn\u2019s disease. Bacteria was visualized using silver stain in human samples, and antibiotics were administered to HLA\u2013B27\u2013transgenic rats. The NLRP3 inhibitor MCC950 was administered to SKG mice, and ileal and joint tissues were assessed by IHC analysis and real\u2010time qRT\u2010PCR. The role of inflammasome in modulating the interleukin\u201023 (IL\u201023)\/IL\u201017 axis was studied ex vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Expression levels of\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      ,\n                      <jats:italic>Nlrc4<\/jats:italic>\n                      , and\n                      <jats:italic>Aim2<\/jats:italic>\n                      were increased in the gut of HLA\u2013B27\u2013transgenic rats and reduced by antibiotic treatment (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). In curdlan\u2010treated SKG mice, NLRP3 blockade prevented ileitis and delayed arthritis onset (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). Compared to healthy controls, AS patients demonstrated overexpression of\n                      <jats:italic>NLRP3<\/jats:italic>\n                      (fold induction 2.33 versus 22.2;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001),\n                      <jats:italic>NLRC4<\/jats:italic>\n                      (fold induction 1.90 versus 6.47;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001),\n                      <jats:italic>AIM2<\/jats:italic>\n                      (fold induction 2.40 versus 20.8;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001),\n                      <jats:italic>CASP1<\/jats:italic>\n                      (fold induction 2.53 versus 24.8;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001),\n                      <jats:italic>IL1B<\/jats:italic>\n                      (fold induction 1.07 versus 10.93;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), and\n                      <jats:italic>IL18<\/jats:italic>\n                      (fold induction 2.56 versus 15.67;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001) in the ileum, and caspase 1 activity was increased (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01). The score of adherent and invasive mucosa\u2010associated bacteria was higher in AS (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.01) and correlated with the expression of inflammasome components in peripheral blood mononuclear cells (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001).\u00a0\n                      <jats:italic>NLRP3<\/jats:italic>\n                      \u00a0expression was associated with disease activity (the Ankylosing Spondylitis Disease Activity Score using the C\u2010reactive protein level) (r\n                      <jats:sup>2<\/jats:sup>\n                      = 0.28,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.01) and\u00a0with\n                      <jats:italic>IL23A<\/jats:italic>\n                      expression (r\n                      <jats:sup>2<\/jats:sup>\n                      = 0.34,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001)\n                      <jats:italic>.\u00a0<\/jats:italic>\n                      In vitro, inflammasome activation in AS monocytes was paralleled by increased serum levels of IL\u20101\u03b2 and IL\u201018. Induction of\n                      <jats:italic>IL23A<\/jats:italic>\n                      ,\n                      <jats:italic>IL17A,<\/jats:italic>\n                      and\n                      <jats:italic>IL22<\/jats:italic>\n                      was IL\u20101\u03b2\u2013dependent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inflammasome activation occurs in rodent models of AS and in AS patients, is associated with dysbiosis, and is involved in triggering ileitis in SKG mice. Inflammasomes drive type III cytokine production with an IL\u20101\u03b2\u2013dependent mechanism in AS patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.41644","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T06:09:55Z","timestamp":1610777395000},"page":"1189-1199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Inflammasome Activation in Ankylosing Spondylitis Is Associated With Gut Dysbiosis"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2479-6958","authenticated-orcid":false,"given":"Giuliana","family":"Guggino","sequence":"first","affiliation":[{"name":"University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9022-8863","authenticated-orcid":false,"given":"Daniele","family":"Mauro","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi della Campania Luigi Vanvitelli  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aroldo","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Ospedali Riuniti Villa Sofia\u2010Cervello  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Alessandro","sequence":"additional","affiliation":[{"name":"University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Raimondo","sequence":"additional","affiliation":[{"name":"University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Sophie","family":"Bergot","sequence":"additional","affiliation":[{"name":"University of Queensland Diamantina Institute and Princess Alexandra Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arifur","family":"Rahman","sequence":"additional","affiliation":[{"name":"University of Queensland Diamantina Institute and Princess Alexandra Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Ellis","sequence":"additional","affiliation":[{"name":"NIHR Guy\u2019s and St Thomas\u2019 Biomedical Research Centre  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Milling","sequence":"additional","affiliation":[{"name":"University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-3092","authenticated-orcid":false,"given":"Rik","family":"Lories","sequence":"additional","affiliation":[{"name":"Katholieke Universiteit Leuven  Leuven 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