Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Recent evidence suggests that systemic autoimmune disease depends on signals from TLR ligands, but little is known about how TLR-dependent pathways lead to the loss of self tolerance in vivo. To address this, we have examined the role of TLR signaling in Lyn-deficient mice, which develop an autoimmune disease similar to SLE. We found that absence of the TLR signaling adaptor molecule MyD88 suppresses plasma cell differentiation of switched and unswitched B cells, and prevents the generation of antinuclear IgG antibodies and glomerulonephritis. In mixed chimeras the increased IgM and IgG antibody secretion in Lyn-deficient mice is at least partially due to B cell-independent effects of Lyn. We now show that MyD88 deficiency blocks the expansion and activation of DC in which Lyn is also normally expressed, and prevents the hypersecretion of proinflammatory cytokines IL-6 and IL-12 by Lyn-deficient DC. These findings further highlight the important role of TLR-dependent signals in both lymphocyte activation and autoimmune pathogenesis.

Original publication

DOI

10.1002/eji.200737293

Type

Journal article

Journal

European journal of immunology

Publication Date

10/2007

Volume

37

Pages

2734 - 2743

Addresses

Henry Wellcome Building of Molecular Physiology, University of Oxford, Oxford, UK.

Keywords

Cells, Cultured, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Autoimmune Diseases, Disease Models, Animal, src-Family Kinases, Autoantibodies, Signal Transduction, Myeloid Differentiation Factor 88