{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:46:36Z","timestamp":1777499196543,"version":"3.51.4"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Leaky gut has been linked to autoimmune disorders including lupus. We previously reported upregulation of anti-flagellin antibodies in the blood of lupus patients and lupus-prone mice, which led to our hypothesis that a leaky gut drives lupus through bacterial flagellin-mediated activation of toll-like receptor 5 (TLR5).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We created MRL\/<jats:italic>lpr<\/jats:italic> mice with global <jats:italic>Tlr5<\/jats:italic> deletion through CRISPR\/Cas9 and investigated lupus-like disease in these mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Contrary to our hypothesis that the deletion of <jats:italic>Tlr5<\/jats:italic> would attenuate lupus, our results showed exacerbation of lupus with <jats:italic>Tlr5<\/jats:italic> deficiency in female MRL\/<jats:italic>lpr<\/jats:italic> mice. Remarkably higher levels of proteinuria were observed in <jats:italic>Tlr5<\/jats:italic><jats:sup>-\/-<\/jats:sup> MRL\/<jats:italic>lpr<\/jats:italic> mice suggesting aggravated glomerulonephritis. Histopathological analysis confirmed this result, and <jats:italic>Tlr5<\/jats:italic> deletion significantly increased the deposition of IgG and complement C3 in the glomeruli. In addition, <jats:italic>Tlr5<\/jats:italic>\u00a0deficiency significantly increased renal infiltration of Th17 and activated cDC1 cells. Splenomegaly and lymphadenopathy were also aggravated in Tlr5<jats:sup>-\/-<\/jats:sup> MRL\/<jats:italic>lpr<\/jats:italic> mice suggesting impact on lymphoproliferation. In the spleen, significant decreased frequencies of regulatory lymphocytes and increased germinal centers were observed with <jats:italic>Tlr5<\/jats:italic> deletion. Notably, <jats:italic>Tlr5<\/jats:italic> deficiency did not change host metabolism or the existing leaky gut; however, it significantly reshaped the fecal microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Global deletion of <jats:italic>Tlr5<\/jats:italic> exacerbates lupus-like disease in MRL\/<jats:italic>lpr<\/jats:italic> mice. Future studies will elucidate the underlying mechanisms by which <jats:italic>Tlr5<\/jats:italic> deficiency modulates host-microbiota interactions to exacerbate lupus.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1359534","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T08:53:51Z","timestamp":1706604831000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["RETRACTED: Tlr5 deficiency exacerbates lupus-like disease in the MRL\/lpr mouse model"],"prefix":"10.3389","volume":"15","author":[{"given":"Razan M.","family":"Alajoleen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David 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