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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,3,31]]},"abstract":"<jats:p>\n                    Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4\n                    <jats:sup>+<\/jats:sup>\n                    CCR6\n                    <jats:sup>+<\/jats:sup>\n                    IL-7R\n                    <jats:sup>+<\/jats:sup>\n                    T cells from human tonsils produced IL-10 following stimulation by na\u00efve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6\n                    <jats:sup>+<\/jats:sup>\n                    B helper T cells were phenotypically distinct from follicular helper T (T\n                    <jats:sub>FH<\/jats:sub>\n                    ) cells and lacked BCL6 expression. In peripheral blood, a CCR6\n                    <jats:sup>+<\/jats:sup>\n                    T cell population with similar characteristics was identified, which lacked Th17- and T\n                    <jats:sub>FH<\/jats:sub>\n                    -associated gene signatures and differentiation-associated surface markers. CD4\n                    <jats:sup>+<\/jats:sup>\n                    CCR6\n                    <jats:sup>+<\/jats:sup>\n                    T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4\n                    <jats:sup>+<\/jats:sup>\n                    CCR6\n                    <jats:sup>+<\/jats:sup>\n                    IL-7R\n                    <jats:sup>+<\/jats:sup>\n                    T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10\u2013producing CCR6\n                    <jats:sup>+<\/jats:sup>\n                    T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1917834117","type":"journal-article","created":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T17:19:39Z","timestamp":1584465579000},"page":"7305-7316","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["Evidence for a pathogenic role of extrafollicular, IL-10\u2013producing CCR6\n                    <sup>+<\/sup>\n                    B helper T cells in systemic lupus erythematosus"],"prefix":"10.1073","volume":"117","author":[{"given":"F.","family":"Facciotti","sequence":"first","affiliation":[{"name":"Autoimmunity Laboratory, National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Larghi","sequence":"additional","affiliation":[{"name":"Autoimmunity Laboratory, National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Bosotti","sequence":"additional","affiliation":[{"name":"Autoimmunity Laboratory, National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Vasco","sequence":"additional","affiliation":[{"name":"Autoimmunity Laboratory, National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Gagliani","sequence":"additional","affiliation":[{"name":"Section of Molecular Immunology and Gastroenterology, Center of Internal Medicine, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;"},{"name":"Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520;"},{"name":"Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;"},{"name":"Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institute and University Hospital, 17176 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2013-0043","authenticated-orcid":false,"given":"C.","family":"Cordiglieri","sequence":"additional","affiliation":[{"name":"Immunology Laboratory, National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Mazzara","sequence":"additional","affiliation":[{"name":"Integrative Biology Laboratory, National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Ranzani","sequence":"additional","affiliation":[{"name":"Integrative Biology Laboratory, National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Rottoli","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Curti","sequence":"additional","affiliation":[{"name":"Integrative Biology Laboratory, National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Penatti","sequence":"additional","affiliation":[{"name":"Azienda Socio Sanitaria Territoriale Gaetano Pini, 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Karnani","sequence":"additional","affiliation":[{"name":"Autoimmunity Laboratory, National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Crosti","sequence":"additional","affiliation":[{"name":"Autoimmunity Laboratory, National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Bombaci","sequence":"additional","affiliation":[{"name":"Immunology Laboratory, National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d 20122 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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