Normal individuals co-exist with vast numbers of commensal microflora in their mucosal tissues without any pathological problems. Abnormality in the establishment or maintenance of such symbiotic relationship can lead to chronic immune responses towards the commensal microflora, and the responses in the gastrointestinal tract can lead to the development of inflammatory bowl diseases (IBD), such as Crohn's disease and ulcerative colitis. A widely used animal model to study IBD is the system of adoptively transferring naive CD4 T cells into syngeneic immunodeficient hosts, which leads to chronic inflammation in the intestines from unregulated T cell responses to enteric commensal microflora antigens. While the disease in this system is efficiently blocked by co-transfer of regulatory T cells (Tregs), the reasons why commensal bacterial antigens become overtly immunogenic in the first place is far from clear. To better understand this issue, the following two areas of investigation are proposed: First, the presence of a novel population of T cells with the ability to regulate enteric antigen presentation will be sought using a strain of severely lymphopenic mice that is resistant to IBD induction. Second, the presence of a population of T cells that can regulate enteric antigen presentation in normal mice will be sought using the information gained from the lymphopenic mice. The results from these studies may be useful in better understanding the etiology of IBD in humans and in the development of new therapeutic approaches for treatment of the disease.

Public Health Relevance

Inflammatory bowel disease (IBD) is a debilitating chronic disease affecting the intestines from unknown causes. This proposal is designed to define the basis for the early events leading to IBD in a mouse model of human IBD. The findings from this proposal may be useful in better understanding the etiology of human IBD and in the development of new therapeutic approaches for treatment of the human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI090610-01
Application #
7982541
Study Section
Cellular and Molecular Immunology - B Study Section (CMIB)
Program Officer
Rothermel, Annette L
Project Start
2010-06-01
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
1
Fiscal Year
2010
Total Cost
$284,850
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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