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.
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.
|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|