Principal Investigator: John McGuire, M.D.
The objective of this project is to evaluate the potential role of regulatory T-cells (Tregs) in the control of pulmonary inflammation induced by P. aeruginosa infection. We proposed that interactions between the adhesion protein E-cadherin and the leukocyte-specific E-cadherin receptor CD103 activate CD103+ dendritic cells to induce a Treg response and an increase in anti-inflammatory IL-10 in the lung after P. aeruginosa infection and hypothesized that disruption of this mechanism in CF could contribute to low IL-10 levels and chronic inflammation in lungs of CF patients. We proposed three aims: (1) Define the role of CD103 and Tregs in P. aeruginosa pneumonia in mice. (2) Evaluate whether Treg numbers and function are impaired in CF mice. (3) Validate these concepts by assessing samples of lung tissues from CF patients.