Systemic Lupus (SLE) is an autoimmune disease characterized by the production of an array of anti- nuclear antibodies that affects women far more frequently than men. Abnormal B and T cell function has been extensively studied in murine models of SLE. We have developed a mouse with a deletion of Blimp-1 function uniquely in dendritic cells. Female mice develop a lupus-like serology while male mice do not. We propose to understand the alterations in dendritic cell function and the mechanism for the subsequent dysregulation of B cell function. Furthermore, we will determine why this genetic defect manifests as autoimmunity only in female mice. These studies will further our understanding of dendritic cell biology and may identify a new therapeutic target in SLE.

Public Health Relevance

Systemic lupus remains a challenging disease to treat and several new therapies brought to the clinic have failed to show efficacy. We propose to study a new model for lupus in the belief that it differs sufficiently from other models but resembles human disease enough to bring us to new therapeutic targets.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Scientist Development Award - Research & Training (K01)
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Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
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Mancini, Marie
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Feinstein Institute for Medical Research
United States
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Son, Myoungsun; Kim, Sun Jung; Diamond, Betty (2016) SLE-associated risk factors affect DC function. Immunol Rev 269:100-17
Kim, Sun Jung (2015) Immunological function of Blimp-1 in dendritic cells and relevance to autoimmune diseases. Immunol Res 63:113-20
Kim, Sun Jung; Diamond, Betty (2015) Modulation of tolerogenic dendritic cells and autoimmunity. Semin Cell Dev Biol 41:49-58
Watchmaker, Payal B; Lahl, Katharina; Lee, Mike et al. (2014) Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice. Nat Immunol 15:98-108
Franchin, Giovanni; Son, Myoungsun; Kim, Sun Jung et al. (2013) Anti-DNA antibodies cross-react with C1q. J Autoimmun 44:34-9
Kim, Sun Jung; Gregersen, Peter K; Diamond, Betty (2013) Regulation of dendritic cell activation by microRNA let-7c and BLIMP1. J Clin Invest 123:823-33
Yan, Yi; Wang, Ying-Hua; Diamond, Betty (2012) IL-6 contributes to an immune tolerance checkpoint in post germinal center B cells. J Autoimmun 38:1-9
Kim, Sun Jung; Zou, Yong Rui; Goldstein, Jordan et al. (2011) Tolerogenic function of Blimp-1 in dendritic cells. J Exp Med 208:2193-9