JCI online early table of contents: Marc...(rize lupus Systemic lupus erythema...),Health

Systemic lupus erythematosus (SLE), commonly known as lupus, is a chronic autoimmune disease characterized by the inflammatory destruction of many organs, including the skin, joints, and kidneys. A hallmark of the disease is the production of IgG antibodies that target nucleic acidassociated proteins in the nucleus of the individuals own cells (so called autoantibodies). A new study, by Paul Utz and colleagues at Stanford University, has now characterized a new pathway by which immune cells known as B cells can be stimulated to produce these IgG autoantibodies in a mouse model of SLE. Specifically, signaling downstream of B cell recognition of soluble factors known as type I IFNs was found to be required for the production of IgG autoantibodies. Further, these signaling pathways were also required to upregulate the expression of two sensors of the nucleic acidassociated proteins recognized by these IgG autoantibodies (TLR7 and TLR9), an event that stimulates production of IgG autoantibodies. The authors therefore suggested that their data provide a clear rationale for pursuing the development of specific inhibitors of type I IFNs and TLRs for the treatment of individuals with SLE, therapies that are currently in preclinical and/or early-stage clinical trials.

TITLE: IRF9 and STAT1 are required for IgG autoantibody production and B cell expression of TLR7 in mice

AUTHOR CONTACT:
Paul J. Utz
Stanford University School of Medicine, Stanford, California, USA.
Phone: (650) 724-5421; Fax: (650) 723-7509; E-mail: pjutz@stanford.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=30065

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