{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T09:27:25Z","timestamp":1793179645480,"version":"4.5.0"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T00:00:00Z","timestamp":1577059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15H06866"],"award-info":[{"award-number":["15H06866"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K10112"],"award-info":[{"award-number":["17K10112"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H05355"],"award-info":[{"award-number":["16H05355"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H05207"],"award-info":[{"award-number":["16H05207"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18KK0228"],"award-info":[{"award-number":["18KK0228"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mochida Memorial Foundation"},{"name":"Japanese Society for Pediatric Endocrinology Future Development"},{"name":"Japanese Society of Hematology Research"},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Gain-of-function (GOF) mutations in the gene for signal transducer and activator of transcription 1 (STAT1) account for approximately one-half of patients with chronic mucocutaneous candidiasis (CMC) disease. Patients with GOF-STAT1 mutations display a broad variety of infectious and autoimmune manifestations in addition to CMC, and those with severe infections and\/or autoimmunity have a poor prognosis. The establishment of safe and effective treatments based on a precise understanding of the molecular mechanisms of this disorder is required to improve patient care. To tackle this problem, we introduced the human R274Q GOF mutation into mice [GOF-Stat1 knock-in (GOF-Stat1R274Q)]. To investigate the immune responses, we focused on the small intestine (SI), which contains abundant Th17 cells. Stat1R274Q\/R274Q mice showed excess phosphorylation of STAT1 in CD4+ T cells upon IFN-\u03b3 stimulation, consistent with the human phenotype in patients with the R274Q mutation. We identified two subpopulations of CD4+ T cells, those with \u2018normal\u2019 or \u2018high\u2019 level of basal STAT1 protein in Stat1R274Q\/R274Q mice. Upon IFN-\u03b3 stimulation, the \u2018normal\u2019 level CD4+ T cells were more efficiently phosphorylated than those from WT mice, whereas the \u2018high\u2019 level CD4+ T cells were not, suggesting that the level of STAT1 protein does not directly correlate with the level of pSTAT1 in the SI. Inoculation of Stat1R274Q\/R274Q mice with Candida albicans elicited decreased IL-17-producing CD4+ROR\u03b3t+ cells. Stat1R274Q\/R274Q mice also excreted larger amounts of C. albicans DNA in their feces than control mice. Under these conditions, there was up-regulation of T-bet in CD4+ T cells. GOF-Stat1R274Q mice thus should be a valuable model for functional analysis of this disorder.<\/jats:p>","DOI":"10.1093\/intimm\/dxz079","type":"journal-article","created":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T20:12:46Z","timestamp":1576699966000},"page":"259-272","source":"Crossref","is-referenced-by-count":27,"title":["Human gain-of-function <i>STAT1<\/i> mutation disturbs IL-17 immunity in mice"],"prefix":"10.1093","volume":"32","author":[{"given":"Moe","family":"Tamaura","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University , Hiroshima, Japan"},{"name":"Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences , Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Satoh-Takayama","sequence":"additional","affiliation":[{"name":"Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences , Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Tsumura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University , Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaharu","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences , Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Goda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University , Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Kageyama","sequence":"additional","affiliation":[{"name":"Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences , Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichi","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University , Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University , Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaki","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University , Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Frontier Research and Development, Kazusa DNA Research Institute , Kisarazu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Koseki","sequence":"additional","affiliation":[{"name":"Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences , Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Ohara","sequence":"additional","affiliation":[{"name":"Department of Applied Genomics, Kazusa DNA Research Institute , Kisarazu, Japan"},{"name":"Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences , Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University , Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ohno","sequence":"additional","affiliation":[{"name":"Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences , Yokohama, Japan"},{"name":"Division of Immunobiology, Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University , Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University , Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,23]]},"reference":[{"key":"2022090619283024600_CIT0001","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/S0140-6736(67)90974-9","article-title":"Chronic mucocutaneous candidiasis, deficiency of delayed 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Immunol"},{"key":"2022090619283024600_CIT0022","doi-asserted-by":"crossref","first-page":"e114","DOI":"10.1038\/cti.2016.71","article-title":"Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity","volume":"5","author":"Okada","year":"2016","journal-title":"Clin. Transl. Immunology"},{"key":"2022090619283024600_CIT0023","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.jaci.2012.11.054","article-title":"Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune dysregulation-polyendocrinopathy-enteropathy-X-linked-like syndrome","volume":"131","author":"Uzel","year":"2013","journal-title":"J. Allergy Clin. Immunol"},{"key":"2022090619283024600_CIT0024","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.jaci.2013.09.032","article-title":"Fatal combined immunodeficiency associated with heterozygous mutation in STAT1","volume":"133","author":"Sharfe","year":"2014","journal-title":"J. Allergy Clin. 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