Anti-ribosomal P protein antibody induces Th1 responses by enhancing the production of IL-12 in activated monocytes
Tatsuo Nagai1 , Tamiko Yanagida2 , Shunsei Hirohata1
8 March 2010
11 August 2010
8 September 2010
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Autoantibodies to ribosomal P proteins (anti-P) are detected in 12-16% of patients with systemic lupus erythematosus (SLE), and have been found to be associated with some manifestations, including lupus psychosis, nephritis and hepatitis. We have recently disclosed that anti-P react with activated human peripheral blood monocytes, and enhance their production of tumor necrosis factor-α and interleukin (IL)-6. It is also possible that anti-P might regulate other monocyte functions, including the regulation of T helper (Th) responses. The current study was therefore undertaken to explore the effects of anti-P on the induction of Th1 responses. Peripheral blood mononuclear cells (PBMC) from healthy donors were cultured with affinity-purified anti-P or control IgG. Highly purified monocytes were cultured with interferon (IFN)-γ in the presence of anti-P or normal IgG. Anti-P significantly enhanced the production of IFN-γ by PBMC. Of note, anti-IL-12 monoclonal antibodies almost completely abrogated the anti-P-mediated upregulation of the IFN-γ production of PBMC. Accordingly, anti-P significantly enhanced the production of IL-12 by activated monocytes. These results indicate that anti-P induce Th1 responses by upregulating the production of IL-12 by activated monocytes. The data therefore suggest that anti-P play an important role in the pathogenesis of SLE through the promotion of Th1 responses.
Anti-ribosomal P protein antibody - IFN-γ - Th1 - IL-12 - Monocyte