We propose that mast cell regulation of immune responses in EAE (and by extension, MS) occurs through several mechanisms. These include: a) alteration of the blood-brain barrier to facilitate entry of autoreactive T cells;b) release of pro-inflammatory cytokines such as TNF-a;c) regulation of T cell trafficking via chemokine expression or modulation of homing receptors;d) release of regulatory cytokines such as IL-4 and IL-10 to modulate an ongoing response;e) and direct damage of the myelin sheath through release of proteases/cytokines that contribute to """"""""epitope spreading"""""""" by releasing new antigen epitopes for presentation to T cells. In this application, we will use an established model of relapsing-remitting multiple sclerosis to examine some of the potential mechanisms that underlie mast cell effects on a disease course.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS054395-04
Application #
7585653
Study Section
Special Emphasis Panel (ZRG1-F07 (20))
Program Officer
Utz, Ursula
Project Start
2006-03-01
Project End
2011-02-28
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
4
Fiscal Year
2009
Total Cost
$56,684
Indirect Cost
Name
Northwestern University at Chicago
Department
Pathology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611