{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:01:19Z","timestamp":1791295279393,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"47","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,11,22]]},"abstract":"<jats:p>Immune suppressive activities exerted by regulatory T-cell subsets have several specific functions, including self-tolerance and regulation of adaptive immune reactions, and their dysfunction can lead to autoimmune diseases and contribute to AIDS and cancer. Two functionally distinct regulatory T-cell subsets are currently identified in peripheral tissues: thymus-developed natural T regulatory cells (nTregs) controlling self-tolerance and antiinflammatory IL-10\u2013secreting type 1 regulatory T cells (Tr1) derived from Ag-stimulated T cells, which regulate inflammation-dependent adaptive immunity and minimize immunopathology. We establish herein that cell contact-mediated nTreg regulatory function is inhibited by inflammation, especially in the presence of the complement C3b receptor (CD46). Instead, as with other T-cell subsets, the latter inflammatory conditions of stimulation skew nTreg differentiation to Tr1 cells secreting IL-10, an effect potentiated by IFN-\u03b1. The clinical relevance of these findings was verified in a study of 152 lupus patients, in which we showed that lupus nTreg dysfunction is not due to intrinsic defects but is rather induced by C3b stimulation of CD46 and IFN-\u03b1 and that these immune components of inflammation are directly associated with active lupus. These results provide a rationale for using anti\u2013IFN-\u03b1 Ab immunotherapy in lupus patients.<\/jats:p>","DOI":"10.1073\/pnas.1113301108","type":"journal-article","created":{"date-parts":[[2011,11,8]],"date-time":"2011-11-08T01:51:56Z","timestamp":1320717116000},"page":"18995-19000","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":52,"title":["IFN-\u03b1 and CD46 stimulation are associated with active lupus and skew natural T regulatory cell differentiation to type 1 regulatory T (Tr1) cells"],"prefix":"10.1073","volume":"108","author":[{"given":"H\u00e9l\u00e8ne","family":"Le Buanec","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U976, Immunologie, Dermatologie, Oncologie, H\u00f4pital Saint-Louis 75010 Paris, France;"},{"name":"Universit\u00e9 Denis Diderot-Paris 7, F-75000 Paris, France;"},{"name":"Antiviral Immunity, Biotherapy, and Vaccine Unit, Infection and Epidemiology Department, Institut Pasteur, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Lise","family":"Gougeon","sequence":"additional","affiliation":[{"name":"Antiviral Immunity, Biotherapy, and Vaccine Unit, Infection and Epidemiology Department, Institut Pasteur, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Mathian","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Interne, Centre de R\u00e9f\u00e9rence National pour les Lupus et le Syndrome des Antiphospholipides, Centre Hospitalier Universitaire Piti\u00e9-Salp\u00eatri\u00e8re, Assistance Publique\u2013H\u00f4pitaux de Paris (APHP), 75013 Paris, France;"},{"name":"Universit\u00e9 Pierre et Marie Curie, 75005 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Lebon","sequence":"additional","affiliation":[{"name":"H\u00f4pital Saint Vincent de Paul-Cochin, APHP, 75014 Paris, France;"},{"name":"Universit\u00e9 Paris Descartes, 75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"Dupont","sequence":"additional","affiliation":[{"name":"Medecine et Innovation, 75007 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Peltre","sequence":"additional","affiliation":[{"name":"Ecole Sup\u00e9rieure de Physique et de Chimie Industrielles, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 7121, 75005 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Hemon","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U976, Immunologie, Dermatologie, Oncologie, H\u00f4pital Saint-Louis 75010 Paris, France;"},{"name":"Universit\u00e9 Denis Diderot-Paris 7, F-75000 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Schmid","sequence":"additional","affiliation":[{"name":"Institut Universitaire d'H\u00e9matologie, Universit\u00e9 Paris 7, 75010 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Bizzini","sequence":"additional","affiliation":[{"name":"Neovacs SA, 75014 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"K\u00fcnding","sequence":"additional","affiliation":[{"name":"Dermatologische Klinik, Universit\u00e4tsSpital Z\u00fcrich, 8091 Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ars\u00e8ne","family":"Burny","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Hematology, Institut Jules Bordet, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium; 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