The investigators have described a new murine model of human SLE. By injection of pristane into BALB/c mice, these mice develop IgM anti-DNA and anti-histone antibodies followed by IgG antibodies with specificities similar to human SLE. They propose that the initial autoantibodies are T-cell-independent and the IgG autoantibodies that develop later, are T-cell-dependent. In the first specific aim, the investigators will study which T-cell subpopulations are responsible for late autoantibody production. They will evaluate autoantibody production in a variety of knock-out mice including B2m, class II, TAP I, CD4, CD8, and specific TCR. In the second specific aim, they will investigate the role of Th1 and Th2 cytokines as they relate to pristane-induced autoantibody production. Cytokines will be quantified by RT-PCR as well as ELISAs. Cytokine examination will be performed in concert with the gene knock-out studies in Specific Aim 1 to determine whether a specific T-cell subset or cytokine is more critical for autoantibody production.
In Aim 3, the investigators will quantify the cytokines produced by macrophages, IL-1, IL-6 and TNF-a. In addition, they will also test whether LPS accelerates autoantibody production. To examine the effect of pristane on T-cell tolerance, pristane will be administered to mice previously immunized with the superantigen, SEB. The numbers of responding cells as well as the production of IL-2 and IL-4 will be quantified.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Immunological Sciences Study Section (IMS)
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Serrate-Sztein, Susana
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University of Florida
Internal Medicine/Medicine
Schools of Medicine
United States
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Han, Shuhong; Zhuang, Haoyang; Shumyak, Stepan et al. (2018) Liver X Receptor Agonist Therapy Prevents Diffuse Alveolar Hemorrhage in Murine Lupus by Repolarizing Macrophages. Front Immunol 9:135
Han, Shuhong; Zhuang, Haoyang; Shumyak, Stepan et al. (2017) A Novel Subset of Anti-Inflammatory CD138+ Macrophages Is Deficient in Mice with Experimental Lupus. J Immunol 199:1261-1274
Zhuang, Haoyang; Han, Shuhong; Lee, Pui Y et al. (2017) Pathogenesis of Diffuse Alveolar Hemorrhage in Murine Lupus. Arthritis Rheumatol 69:1280-1293
Zhuang, Haoyang; Han, Shuhong; Li, Yi et al. (2016) A Novel Mechanism for Generating the Interferon Signature in Lupus: Opsonization of Dead Cells by Complement and IgM. Arthritis Rheumatol 68:2917-2928
Shumyak, Stepan; Yang, Li-Jun; Han, Shuhong et al. (2016) ""Lupoid hepatitis"" in SLE patients and mice with experimental lupus. Clin Immunol 172:65-71
Han, Shuhong; Zhuang, Haoyang; Xu, Yuan et al. (2015) Maintenance of autoantibody production in pristane-induced murine lupus. Arthritis Res Ther 17:384
Xu, Yuan; Zhuang, Haoyang; Han, Shuhong et al. (2015) Mechanisms of tumor necrosis factor ? antagonist-induced lupus in a murine model. Arthritis Rheumatol 67:225-37
Reeves, Westley H (2014) Editorial: systemic lupus erythematosus: death by fire and ICE? Arthritis Rheumatol 66:6-9
Pawar, Rahul D; Goilav, Beatrice; Xia, Yumin et al. (2014) Serum autoantibodies in pristane induced lupus are regulated by neutrophil gelatinase associated lipocalin. Clin Immunol 154:49-65
Zhuang, Haoyang; Han, Shuhong; Xu, Yuan et al. (2014) Toll-like receptor 7-stimulated tumor necrosis factor ? causes bone marrow damage in systemic lupus erythematosus. Arthritis Rheumatol 66:140-51

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