Immune mediated disease such as inflammatory bowel disease (IBD) is the result of the inappropriate T cell response. There are voids in our understanding of how T cells integrate g-protein mediated chemotactic and chemokinetic """"""""go"""""""" signals with T cell antigen receptor """"""""stop"""""""" signals. Together these signals result in the appropriate T cell response to stimuli. Using the powerful technology of intravital laser scanning confocal microscopy, along with fluorescently labeled T cells and dendritic cells (DC), we aim to define the biophysical dynamics of T-DC interactions in vivo. Next, we aim to define how defects in T cell """"""""stop"""""""" versus """"""""go"""""""" integration, resulting from a null mutation in the g-protein subunit G-alphai2, leads to altered T cell biophysical dynamics and therefore, susceptibility to T cell mediated IBD. Next, we aim to examine how regulatory cells may correct T cell dynamics in G-alphai2 null T cells leading to protection from disease onset and progression. The long-term goal is to therapeutically modulate T cell """"""""stop"""""""" versus """"""""go"""""""" signals to abrogate disease development and progression. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK078153-03
Application #
7479647
Study Section
Special Emphasis Panel (ZRG1-F07-L (20))
Program Officer
Podskalny, Judith M,
Project Start
2006-09-01
Project End
2009-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
3
Fiscal Year
2008
Total Cost
$50,428
Indirect Cost
Name
New York University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Xu, Cassie; Shen, Yuelei; Littman, Dan R et al. (2012) Visualization of mucosal homeostasis via single- and multiphoton intravital fluorescence microscopy. J Leukoc Biol 92:413-9
Velázquez, Peter; Dustin, Michael L; Nelson, Peter J (2009) Renal dendritic cells: an update. Nephron Exp Nephrol 111:e67-71
Velazquez, Peter; Cameron, Thomas O; Kinjo, Yuki et al. (2008) Cutting edge: activation by innate cytokines or microbial antigens can cause arrest of natural killer T cell patrolling of liver sinusoids. J Immunol 180:2024-8
Velazquez, Peter; Waite, Janelle C; Dustin, Michael L (2007) Dynamics of host defense: the view at the front lines. Nat Immunol 8:1153-7