The intestine is the central organ for uptake of fluids and nutrients, but it is also the largest immune organ. Nowhere in the body has the immune system evolved more regulatory mechanisms to allow for potent and effective immune protection while maintaining the integrity of the mucosal barrier. In mice, several subsets of mucosal regulatory immune cells have been identified. They include the CD8((+ TCR(( intra epithelial lymphocytes (IEL), the mucosal CD8((+plasmacytoid DCs (pDCs) and CD8((+CD4+ TCR((+IEL. The conditions that lead to the differentiation of these mucosal regulatory cells and the mechanisms they employ to orchestrate immune regulation, are poorly defined or not known. In this study we propose to investigate and elucidate differentiation, function and cross communication of mucosal immune regulatory cells. In the first Aim we will define regulatory mechanisms engaged by the SP CD8((+ IEL to communicate immune regulation to other cells. In the second Aim we will investigate the regulatory role of mucosal DCs, and in the third Aim will focus on the regulatory DP CD4CD8(( TCR(( IEL. All of these mucosal regulatory cells uniformly express CD8((. Based on our previous published findings supported by this grant, that CD8(( can act as a modulator of activation signals leading to shifts in cytokine production, survival and differentiation of the triggered cell, we propose to further investigate in this study if CD8(( on these regulatory cells might play key roles for their function and/or survival. Mucosal regulatory cells, which allow for effective immune protection of the intestine without destruction of this vital organ, ultimately control the wellbeing of the whole organism. Understanding mucosal immune regulation will undoubtedly impact our knowledge to advance medical treatments not only for intestinal related diseases but for health improvement in general. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI050265-05A1
Application #
7092889
Study Section
Immunity and Host Defense Study Section (IHD)
Program Officer
Rothermel, Annette L
Project Start
2001-07-01
Project End
2011-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
5
Fiscal Year
2006
Total Cost
$276,791
Indirect Cost
Name
La Jolla Institute
Department
Type
DUNS #
603880287
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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