The objective of this proposal is to define the mechanisms regulating the resolution of a granulomatous form of experimental autoimmune thyroiditis (G-EAT) in mice. The proposed studies will investigate the role of cell surface expressed co-stimulatory molecules and cytokines in mediating resolution of G-EAT. Additionally, the investigators that know CD8+T cells play a role in G-EAT resolution, but little information is currently known regarding the cell subsets present in thyroid infiltrates following the peak of disease and what, if any, role particular cells might play in mediating resolution of G-EAT. The proposed studies will identify cell subsets in the thyroid following disease peak, characterize changes in these cell phenotypes during resolution and attempt to determine what, if any, role these cells might play in mediating resolution of G-EAT. This murine G-EAT model provides an excellent opportunity to increase our understanding of organ specific autoimmune diseases and their underlying mechanisms. Also, it will give them insight into the mechanisms by which this same autoimmune response is arrested in a highly specific and targeted manner to result in spontaneous healing of the target organ. Knowledge gained from these studies will be useful in designing therapies to promote resolution or prevent destructive inflammatory responses. Information generated as a result of these studies would be potentially applicable in clinical situations for promoting resolution, not only of autoimmune thyroiditis but also for other autoimmune diseases, by activating pathways which mediate healing.
