The goal of this proposal is to further investigate the hypothesis that CD1d-restricted NKT cells exert a negative regulatory role over MZB cells. This mechanism might play a central role in the maintenance of tolerance, and its deregulation could be involved in triggering or sustaining autoimmunity as suggested by animal models of diabetes and experimental allergic encephalitis (EAE). Preliminary data from Dr. Porcelli's lab indicate that NKT/MZB cell interaction may also play a key role in preventing the development of humoral autoimmunity, such as that which is characteristic of lupus. MZB cells have been shown to be an important source of autoreactive pathogenic antibodies in lupus, and a variety of studies indicate that the NK T cells that may regulate this B cell population is defective in mice that are predisposed to develop SLE. The proposed study will assess the influence of NK T cells on the responses of MZB cells against well characterized T-independent (TI-2) antigens. This approach will allow a detailed series of experiments to investigate the potential role of NKT cells over MZB cells. A series of in vitro and in vivo analyses using TI-2 antigens to challenge C57BL/6 mice will be performed and compared to results in lupus prone mice (NZB/W F1) and NKT deficient (Jalpha281 KO) mice. Finally, it is predicted that NKT cells could prove to be a potential therapeutic target for some autoimmune diseases including lupus, and this hypothesis will be tested by using artificial activators of NKT cells and investigating their effect in MZB activation by T1-2 antigens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI058520-03
Application #
7056083
Study Section
Special Emphasis Panel (ZRG1-F07 (20))
Program Officer
Prograis, Lawrence J
Project Start
2005-03-01
Project End
2007-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
3
Fiscal Year
2006
Total Cost
$55,852
Indirect Cost
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Franchin, Giovanni; Son, Myoungsun; Kim, Sun Jung et al. (2013) Anti-DNA antibodies cross-react with C1q. J Autoimmun 44:34-9