{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:58:19Z","timestamp":1772456299969,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,7,27]],"date-time":"2016-07-27T00:00:00Z","timestamp":1469577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Japan Society for the Promotion of Science (Grant in Aid for Scientific Research","award":["26893198"],"award-info":[{"award-number":["26893198"]}]},{"name":"NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant)","award":["5R01-AR-064350-03"],"award-info":[{"award-number":["5R01-AR-064350-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The recruitment of interleukin\u201017 (IL\u201017)\u2013producing T helper (Th17) cells to inflammatory sites has been implicated in the development of organ damage in inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE). To define the mechanism of calcium\/calmodulin\u2010dependent kinase IV (CaMKIV) activation of Th17 cell recruitment to target tissues, we performed anti\u2013glomerular basement membrane antibody\u2013induced glomerulonephritis (AIGN) experiments in mice and studied samples from patients with SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We induced experimental AIGN in CaMKIV\u2010sufficient or CaMKIV\u2010deficient mice and compared histology, Th17 cell\u2013related chemokine expression, and numbers of IL\u201017\u2013producing cells in kidneys. We also evaluated the efficacy of the CaMKIV inhibitor KN\u201093 in AIGN\u2010induced kidney disease. The expression of CCR6 in memory CD4+ T cells before AIGN induction was analyzed by flow cytometry. We investigated the correlation between CCR6 expression in peripheral blood and the severity of glomerulonephritis in patients with SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CaMKIV\u2010deficient mice displayed less glomerular injury after induction of AIGN. Kidney infiltration by IL\u201017\u2013producing CD4+ T cells along with CCR6 and CCL20 expression were significantly decreased in CaMKIV\u2010deficient mice. Similarly, treatment of mice with KN\u201093 improved clinical and pathologic outcomes. Expression and function of CCR6 in peripheral blood memory CD4+ T cells was decreased in CaMKIV\u2010deficient mice. Expression of CCR6 correlated positively with severity of organ damage in SLE patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CaMKIV inhibition represents a novel therapeutic strategy for treatment of Th17 cell\u2013mediated tissue damage in inflammatory diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39665","type":"journal-article","created":{"date-parts":[[2016,3,6]],"date-time":"2016-03-06T02:39:54Z","timestamp":1457231994000},"page":"1981-1988","source":"Crossref","is-referenced-by-count":48,"title":["Calcium\/Calmodulin\u2010Dependent Kinase IV Facilitates the Recruitment of Interleukin\u201017\u2013Producing Cells to Target Organs Through the CCR6\/CCL20 Axis in Th17 Cell\u2013Driven Inflammatory Diseases"],"prefix":"10.1002","volume":"68","author":[{"given":"Tomohiro","family":"Koga","sequence":"first","affiliation":[{"name":"Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, and Nagasaki University 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