{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T22:38:12Z","timestamp":1781303892039,"version":"3.54.1"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,5,22]],"date-time":"2017-05-22T00:00:00Z","timestamp":1495411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/J006742\/1"],"award-info":[{"award-number":["MR\/J006742\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["17966\/Z\/2008"],"award-info":[{"award-number":["17966\/Z\/2008"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>IFN\u2010\u03b3\u2010producing T helper 1 (Th1) cell responses mediate protection against infections but uncontrolled Th1 activity also contributes to a broad range of autoimmune diseases. Autocrine complement activation has recently emerged as key in the induction and contraction of human Th1 immunity: activation of the complement regulator CD46 and the C3aR expressed by CD4<jats:sup>+<\/jats:sup> T cells via autocrine generated ligands C3b and C3a, respectively, are critical to IFN\u2010\u03b3 production. Further, CD46\u2010mediated signals also induce co\u2010expression of immunosuppressive IL\u201010 in Th1 cells and transition into a (self)\u2010regulating and contracting phase. In consequence, C3 or CD46\u2010deficient patients suffer from recurrent infections while dysregulation of CD46 signaling contributes to Th1 hyperactivity in rheumatoid arthritis and multiple sclerosis. Here, we report a defect in CD46\u2010regulated Th1 contraction in patients with systemic lupus erythematosus (SLE). We observed that MMP\u20109\u2010mediated increased shedding of soluble CD46 by Th1 cells was associated with this defect and that inhibition of MMP\u20109 activity normalized release of soluble CD46 and restored Th1 contraction in patients\u2019 T cells. These data may deliver the first mechanistic explanation for the increased serum CD46 levels observed in SLE patients and indicate that targeting CD46\u2010cleaving proteases could be a novel avenue to modulate Th1 responses.<\/jats:p>","DOI":"10.1002\/eji.201646822","type":"journal-article","created":{"date-parts":[[2017,4,26]],"date-time":"2017-04-26T08:00:31Z","timestamp":1493193631000},"page":"1200-1210","source":"Crossref","is-referenced-by-count":43,"title":["Dysregulated CD46 shedding interferes with Th1\u2010contraction in systemic lupus erythematosus"],"prefix":"10.1002","volume":"47","author":[{"given":"Ursula","family":"Ellinghaus","sequence":"first","affiliation":[{"name":"Division of Genetics and Molecular Medicine Department of Medical and Molecular Genetics King's College London Guy's Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cortini","sequence":"additional","affiliation":[{"name":"Division of Genetics and Molecular Medicine Department of Medical and Molecular Genetics King's College London Guy's Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Pinder","sequence":"additional","affiliation":[{"name":"Division of Genetics and Molecular Medicine Department of Medical and Molecular Genetics King's College London Guy's Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaelle","family":"Le\u00a0Friec","sequence":"additional","affiliation":[{"name":"MRC Centre for Transplantation Division of Transplant Immunology and Mucosal Biology King's College London  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Kemper","sequence":"additional","affiliation":[{"name":"MRC Centre for Transplantation Division of Transplant Immunology and Mucosal Biology King's College London  UK"},{"name":"Laboratory of Molecular Immunology and the Immunology Center National Heart, Lung, and Blood Institute (NHLBI) National Institutes of Health (NIH)  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1123-1464","authenticated-orcid":false,"given":"Timothy J.","family":"Vyse","sequence":"additional","affiliation":[{"name":"Division of Genetics and Molecular Medicine Department of Medical and Molecular Genetics King's College London Guy's Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1100359"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/432595"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2010.0126"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115843"},{"key":"e_1_2_8_6_1","first-page":"123","article-title":"Interferon\u2010gamma and systemic autoimmunity","volume":"16","author":"Pollard K. 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