{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T13:13:29Z","timestamp":1761311609754,"version":"3.37.3"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T00:00:00Z","timestamp":1584403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"grant in Aid for Scientific Research","award":["16K09651"],"award-info":[{"award-number":["16K09651"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>We previously reported that fibroblast growth factor 23 (FGF23)\u2010klotho signaling plays a role in B cell immunity. Despite high serum levels of FGF23, a decline in immunity is frequently observed in patients on hemodialysis (HD); thus, abnormalities in the FGF23\u2010klotho signaling pathway in immune cells may occur in these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the number of klotho\u2010positive cells in peripheral blood mononuclear cells from 10 male and 6 female patients on HD and 5 healthy male subjects using flow cytometry. We analyzed the abundance of cleaved klotho protein in the murine B cell line, A20, and in the serum of HD patients and healthy subjects (HS) using flow cytometry and Western blotting. The serum level of A disintegrin and metalloprotease 17 (ADAM17) was measured in HD patients and HS using enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The number of klotho\u2010positive B cells was reduced in HD patients. Serum ADAM17 was responsible for the reduction in klotho, as a specific ADAM17 inhibitor reversed this change. The total serum levels of ADAM17 were similar in HD patients and HS; however, activated ADAM17 was increased in the serum of HD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We concluded that abnormal ADAM17 activation could contribute to the immunocompromised status in patients on HD, in line with the reported role of ADAM17 as an anti\u2010inflammatory and immunosuppressive factor.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.298","type":"journal-article","created":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T08:30:09Z","timestamp":1584433809000},"page":"228-235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Excessive ADAM17 activation occurs in uremic patients and may contribute to their immunocompromised status"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6147-9153","authenticated-orcid":false,"given":"Mitsuru","family":"Yashiro","sequence":"first","affiliation":[{"name":"Department of Nephrology Wakayama Medical University  Wakayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Ohya","sequence":"additional","affiliation":[{"name":"Department of Nephrology Wakayama Medical University  Wakayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Mima","sequence":"additional","affiliation":[{"name":"Department of Nephrology Wakayama Medical University  Wakayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Nephrology Wakayama Medical University  Wakayama 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