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C1q restrains autoimmunity and viral infection by regulating CD8+ T cell metabolism

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Title: C1q restrains autoimmunity and viral infection by regulating CD8+ T cell metabolism
Authors: Ling, GS
Crawford, G
Buang, N
Bartok, I
Tian, K
Thielens, NM
Bally, I
Harker, JA
Ashton-Rickardt, PG
Rutschmann, S
Strid, J
Botto, M
Item Type: Journal Article
Abstract: Deficiency 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.
Issue Date: 4-May-2018
Date of Acceptance: 14-Mar-2018
URI: http://hdl.handle.net/10044/1/59092
DOI: 10.1126/science.aao4555
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science
Start Page: 558
End Page: 563
Journal / Book Title: Science
Volume: 360
Issue: 6388
Copyright Statement: © 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)
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Wellcome Trust
Wellcome Trust
Funder's Grant Number: 101372/Z/13/Z
100999/Z/13/Z
108008/Z/15/Z
108008/Z/15/Z
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
SYSTEMIC-LUPUS-ERYTHEMATOSUS
GRANZYME-B
COMPLEMENT
DISEASE
IMMUNITY
MICE
INFLAMMATION
LYMPHOCYTES
PROGNOSIS
MOLECULE
Animals
Autoantibodies
Autoimmunity
CD8-Positive T-Lymphocytes
Complement C1q
Complement C3
Complement Pathway, Classical
Disease Models, Animal
Immunoglobulins
Immunologic Memory
Lupus Erythematosus, Systemic
Lymphocytic Choriomeningitis
Mice
Mice, Mutant Strains
CD8-Positive T-Lymphocytes
Animals
Mice
Mice, Mutant Strains
Lymphocytic Choriomeningitis
Lupus Erythematosus, Systemic
Disease Models, Animal
Immunoglobulins
Autoantibodies
Autoimmunity
Complement Pathway, Classical
Immunologic Memory
Complement C3
Complement C1q
General Science & Technology
Publication Status: Published
Conference Place: United States
Appears in Collections:Department of Immunology and Inflammation
National Heart and Lung Institute
Faculty of Medicine