Ling, Guang ShengGuang ShengLingCrawford, GregGregCrawfordBuang, NorzawaniNorzawaniBuangBartok, IstvanIstvanBartokTian, KunyuanKunyuanTianThielens, Nicole MNicole MThielensBally, IsabelleIsabelleBallyHarker, James AJames AHarkerAshton-Rickardt, Philip GPhilip GAshton-RickardtRutschmann, SophieSophieRutschmannStrid, JessicaJessicaStridBotto, MarinaMarinaBotto2018-05-142018-05-042018-05-142018-05-04Science, 2018, 360 (6388), pp.558-5630036-8075http://hdl.handle.net/10044/1/59092Deficiency of C1q, the initiator of the complement classical pathway, is associated with the development of systemic lupus erythematosus (SLE). Explaining this association in terms of abnormalities in the classical pathway alone remains problematic because C3 deficiency does not predispose to SLE. Here, using a mouse model of SLE, we demonstrate that C1q, but not C3, restrains the response to self-antigens by modulating the mitochondrial metabolism of CD8+ T cells, which can themselves propagate autoimmunity. C1q deficiency also triggers an exuberant effector CD8+ T cell response to chronic viral infection leading to lethal immunopathology. These data establish a link between C1q and CD8+ T cell metabolism and may explain how C1q protects against lupus, with implications for the role of viral infections in the perpetuation of autoimmunity.© 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works http://www.sciencemag.org/about/science-licenses-journal-article-reuseThis is an article distributed under the terms of the Science Journals Default License (http://www.sciencemag.org/about/science-licenses-journal-article-reuse?_ga=2.266038863.158180865.1526294369-1429968721.1525769942)Science & TechnologyMultidisciplinary SciencesScience & Technology - Other TopicsSYSTEMIC-LUPUS-ERYTHEMATOSUSGRANZYME-BCOMPLEMENTDISEASEIMMUNITYMICEINFLAMMATIONLYMPHOCYTESPROGNOSISMOLECULEAnimalsAutoantibodiesAutoimmunityCD8-Positive T-LymphocytesComplement C1qComplement C3Complement Pathway, ClassicalDisease Models, AnimalImmunoglobulinsImmunologic MemoryLupus Erythematosus, SystemicLymphocytic ChoriomeningitisMiceMice, Mutant StrainsCD8-Positive T-LymphocytesAnimalsMiceMice, Mutant StrainsLymphocytic ChoriomeningitisLupus Erythematosus, SystemicDisease Models, AnimalImmunoglobulinsAutoantibodiesAutoimmunityComplement Pathway, ClassicalImmunologic MemoryComplement C3Complement C1qGeneral Science & TechnologyJournal Articlehttps://www.dx.doi.org/10.1126/science.aao4555101372/Z/13/Z100999/Z/13/Z108008/Z/15/Z108008/Z/15/Z1095-9203