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We address this by using an unbiased activity\u2010based kinome screen of murine lupus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An unbiased activity\u2010based kinome screen (ABKS) of 196 kinases was applied to two genetically different murine lupus strains. Systemic and renal lupus were evaluated following <jats:italic>in\u2009vivo<\/jats:italic> PLK1blockade. The upstream regulators and downstream targets of PLK1 were also interrogated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Multiple signalling cascades were noted to be more active in murine lupus spleens, including PLK1. <jats:italic>In vivo<\/jats:italic> administration of a PLK1\u2010specific inhibitor ameliorated splenomegaly, anti\u2010dsDNA antibody production, proteinuria, BUN and renal pathology in MRL.<jats:italic>lpr<\/jats:italic> mice (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Serum IL\u20106, IL\u201017 and kidney injury molecule 1 (KIM\u20101) were significantly decreased after PLK1 inhibition. PLK1 inhibition reduced germinal centre and marginal zone B cells in the spleen, but changes in T cells were not significant. <jats:italic>In vitro<\/jats:italic>, splenocytes were treated with anti\u2010mouse CD40 Ab or F(ab\u2019)2 fragment anti\u2010mouse IgM. After 24\u2010h stimulation, IL\u20106 secretion was significantly reduced upon PLK1 blockade, whereas IL\u201010 production was significantly increased. The phosphorylation of mTOR was assessed in splenocyte subsets, which revealed a significant change in myeloid cells. PLK1 blockade reduced phosphorylation associated with mTOR signalling, while Aurora\u2010A emerged as a potential upstream regulator of PLK1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The Aurora\u2010A\u2009\u2192\u2009PLK1\u2009\u2192\u2009mTOR signalling axis may be central in lupus pathogenesis, and emerges as a potential therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1362","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T12:00:30Z","timestamp":1641470430000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of polo\u2010like kinase 1 as a therapeutic target in murine lupus"],"prefix":"10.1002","volume":"11","author":[{"given":"Yaxi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Houston Houston TX 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