Follicle-associated epithelium (FAE) is a crucial part of the mucosal immune barrier. It contains M cells that are unique in their ability to deliver pathogens to the organized lymphoid tissues. M cells are necessary for induction of the immune response to enteral pathogens, and they also serve as entrance gates for pathogens such as Shigella, Salmonella, M. tuberculosis, and retroviruses. The current application is based on the discovery of the importance of B cells for the development of FAE and M cells, and is focused on further exploration of this relationship. The goal is to characterize the signals involved in the molecular cross-talk between B cells and epithelial cells within the FAB. The application contains two Specific Aims.
Specific Aim 1 proposes to use imaging of live FAE to study the kinetics of the development of FAE and the generation and maintenance of M cells upon transfer of labeled B lymphocytes.
Specific Aim 2 is designed to identify signal(s) that B lymphocytes provide to epithelial cells to drive the development of FAE and M cells. The design includes transfer of bone marrow from mice with targeted disruption of TNF-family cytokine genes into B cell-deficient recipients and testing of a hypothesis that I lateral inhibition mechanism of tissue differentiation may be involved in the generation of FAE and M cell. The significance of the proposed research program is that it aims at the identification of molecular mechanisms driving development and function of FAE. These mechanisms are critical for protection against pathogens and development of oral vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI052210-05
Application #
7213672
Study Section
Immunobiology Study Section (IMB)
Program Officer
Rothermel, Annette L
Project Start
2002-08-01
Project End
2008-05-31
Budget Start
2005-10-03
Budget End
2008-05-31
Support Year
5
Fiscal Year
2005
Total Cost
$203,333
Indirect Cost
Name
University of Chicago
Department
Pathology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Krebs, Luke T; Starling, Christa; Chervonsky, Alexander V et al. (2010) Notch1 activation in mice causes arteriovenous malformations phenocopied by ephrinB2 and EphB4 mutants. Genesis 48:146-50
Mach, Julie; Hshieh, Tammy; Hsieh, Dennis et al. (2005) Development of intestinal M cells. Immunol Rev 206:177-89