Chronic inflammation mediated by Th2-type cytokines can lead to morbidity and mortality in allergy/asthma. Therefore, one of our major research goals has been to understand the immunological mechanisms controlling Th2 response development, and to design effective immunotherapies to treat or prevent such reactions. In particular, we are interested in understanding how chronic allergic disease leads to tissue remodeling and fibrosis. The development of fibrous tissue is part of the normal process of healing after injury. Nevertheless, in some circumstances, there is a destructive accumulation of excess collagen that interferes with the normal function of the affected tissue. Although there is a great deal of mechanistic information regarding the process of scar tissue formation, there are still large gaps in our understanding of the role of inflammatory cells and cytokines in initiating the fibrotic process. We have been using a mouse model of chronic Ascaris infection to mimic the tissue remodeling seen in models of chronic asthma infection. We are hoping that elucidating the mechanisms leading to tissue pathology and fibrosis may lead to more effective strategies for immunological intervention in this and a variety of other chronic diseases. We are also hoping to use some of the new imaging technology including MRI and CT to visualize changes in mouse lungs over time in our fibrosis studies. If we are able to assess gradual changes in fibrosis and lung structure, we will use such techniques with some of our knockout and transgenic mice to see how different genes effect tissue remodeling. In addition, we have examined the role of other cytokines such as IL-21 and TSLP in the development of tissue remodeling and resultant asthmatic response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000890-05
Application #
7196683
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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Milner, Joshua D; Ward, Jerrold M; Keane-Myers, Andrea et al. (2007) Lymphopenic mice reconstituted with limited repertoire T cells develop severe, multiorgan, Th2-associated inflammatory disease. Proc Natl Acad Sci U S A 104:576-81
McConchie, Brittany W; Norris, Hillary H; Bundoc, Virgilio G et al. (2006) Ascaris suum-derived products suppress mucosal allergic inflammation in an interleukin-10-independent manner via interference with dendritic cell function. Infect Immun 74:6632-41
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