{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T18:55:10Z","timestamp":1793472910446,"version":"4.5.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,24]]},"abstract":"<jats:p>\n                    IL-17\u2013producing CD4\n                    <jats:sup>+<\/jats:sup>\n                    T helper (Th17) cells have recently been defined as a unique subset of proinflammatory helper cells whose development depends on signaling initiated by IL-6 and TGF-\u03b2, autocrine activity of IL-21, activation of STAT3, and induction of the orphan nuclear receptor ROR\u03b3t. The maintenance, expansion, and further differentiation of the committed Th17 cells depend on IL-1\u03b2 and IL-23. IL-17 was originally found produced by circulating human CD45RO\n                    <jats:sup>+<\/jats:sup>\n                    memory T cells. A recent study found that human Th17 memory cells selectively express high levels of CCR6. In this study, we report that human peripheral blood and lymphoid tissue contain a significant number of CD4\n                    <jats:sup>+<\/jats:sup>\n                    FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    T cells that express CCR6 and have the capacity to produce IL-17 upon activation. These cells coexpress FOXP3 and ROR\u03b3t transcription factors. The CD4\n                    <jats:sup>+<\/jats:sup>\n                    FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    CCR6\n                    <jats:sup>+<\/jats:sup>\n                    IL-17\u2013producing cells strongly inhibit the proliferation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    responder T cells. CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>high<\/jats:sup>\n                    -derived T-cell clones express FOXP3, ROR\u03b3t, and IL-17 and maintain their suppressive function via a cell-cell contact mechanism. We further show that human CD4\n                    <jats:sup>+<\/jats:sup>\n                    FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    CCR6\n                    <jats:sup>\u2212<\/jats:sup>\n                    regulatory T (Treg) cells differentiate into IL-17 producer cells upon T-cell receptor stimulation in the presence of IL-1\u03b2, IL-2, IL-21, IL-23, and human serum. This, together with the finding that human thymus does not contain IL-17\u2013producing Treg cells, suggests that the IL-17\n                    <jats:sup>+<\/jats:sup>\n                    FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    Treg cells are generated in the periphery. IL-17\u2013producing Treg cells may play critical roles in antimicrobial defense, while controlling autoimmunity and inflammation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0900408106","type":"journal-article","created":{"date-parts":[[2009,3,9]],"date-time":"2009-03-09T21:39:22Z","timestamp":1236634762000},"page":"4793-4798","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":628,"title":["Identification of IL-17-producing FOXP3\n                    <sup>+<\/sup>\n                    regulatory T cells in humans"],"prefix":"10.1073","volume":"106","author":[{"given":"Kui Shin","family":"Voo","sequence":"first","affiliation":[{"name":"Departments of aImmunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui-Hsi","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of aImmunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio R.","family":"Santori","sequence":"additional","affiliation":[{"name":"The Howard Hughes Medical Institute, The Kimmel Center for Biology and Medicine of The Skirball Institute, New York University School of Medicine, New York, NY 10016; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Boggiano","sequence":"additional","affiliation":[{"name":"The Howard Hughes Medical Institute, The Kimmel Center for Biology and Medicine of The Skirball Institute, New York University School of Medicine, New York, NY 10016; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of aImmunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Arima","sequence":"additional","affiliation":[{"name":"Departments of aImmunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bover","sequence":"additional","affiliation":[{"name":"Departments of aImmunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shino","family":"Hanabuchi","sequence":"additional","affiliation":[{"name":"Departments of aImmunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahan","family":"Khalili","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation and Cellular Therapy, Center for Cancer Immunology Research, The University of Texas M. 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Anderson Cancer Center, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Marinova","sequence":"additional","affiliation":[{"name":"Department of Immunology, Baylor College of Medicine, Houston, TX 77303"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Immunology, Baylor College of Medicine, Houston, TX 77303"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan R.","family":"Littman","sequence":"additional","affiliation":[{"name":"The Howard Hughes Medical Institute, The Kimmel Center for Biology and Medicine of The Skirball Institute, New York University School of Medicine, New York, NY 10016; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of aImmunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.6.2593"},{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"5483","DOI":"10.4049\/jimmunol.155.12.5483","article-title":"Human IL-17: A novel cytokine derived from T cells","volume":"155","author":"Yao Z","year":"1995","unstructured":"Z Yao, et al., Human IL-17: A novel cytokine derived from T cells. 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