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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AR059378-05
Application #
8683106
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Mancini, Marie
Project Start
2010-07-02
Project End
2015-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
City
Manhasset
State
NY
Country
United States
Zip Code
11030
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
Kim, Sun Jung; Goldstein, Jordan; Dorso, Kimberly et al. (2014) Expression of Blimp-1 in dendritic cells modulates the innate inflammatory response in dextran sodium sulfate-induced colitis. Mol Med 20:707-19
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