Anti-ribosomal P protein antibody induces Th1 responses by enhancing the production of IL-12 in activated monocytes.
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.
Nagai
Tatsuo
T
Department of Rheumatology and Infectious Disease, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa, 228-8555, Japan. tnagai-tky@umin.net
Yanagida
Tamiko
T
Hirohata
Shunsei
S
D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001323:Autoantibodies / Q000494:pharmacology*; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation; D012269:Ribosomal Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D012269:Ribosomal Proteins; C054675:ribosomal protein P0; D018664:Interleukin-12; D007371:Interferon-gamma