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 #
5K01AR059378-04
Application #
8492043
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
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$127,711
Indirect Cost
$9,460
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030
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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
Franchin, Giovanni; Son, Myoungsun; Kim, Sun Jung et al. (2013) Anti-DNA antibodies cross-react with C1q. J Autoimmun 44:34-9