Department of Medicine
University of Pittsburgh
Immunologic Mediators of Tissue Destruction in Obstructive Lung Diseases
TRAINEE
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| Yvonne Chan, M.D. |
MENTORS
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| Jay Kolls, M.D. | Anuradha Ray, PhD |
STUDY DESCRIPTION
Recurrent or chronic infection is often accompanied by airway and tissue damage. Although the precise mechanism is unknown, there is emerging evidence that the host immunologic response plays an important role. IL-17 is a T-cell derived cytokine that is crucial in host defense against infection. IL-17 may cause oxidative injury to the airways and lung parenchyma through its effects on neutrophil recruitment.
We hypothesize that chronic infection leads to antigen specific IL-17-producing T cells (Th17) in both draining lymph nodes and lung parenchyma. Furthermore, we predict that these cells will also produce IL-17F and IL-22.
Using lung explant tissue from cystic fibrosis patients as the model for chronic infectious inflammation, this project has the following specific aims:
- Identify the precursor frequency of Pseudomonas aeruginosa (PA)-specific CD4+ Th1, Th2, and Th17 cells
- Determine the role of IL-23, IL-1beta, and IL-21 in the maintenance of human P. aeruginosa-specific CD4+ Th17 cells in human lung. In this series of experiments we investigate if antibodies directed against IL-23, IL-1beta, and/or IL-21 affect Th17 cell recall responses to PA antigens.
This project has led to publications in Nature Medicine and Nature Reviews. Dr. Chan is the recipient of an NIH-funded K08 award and the Howard Hughes Medical Institute Early Career Physician-Scientist Award.