Interleukin-10 Promotes Resolution of Granulomatous Experimental Autoimmune Thyroiditis

Yujiang Fang^*, Gordon C. Sharp^* and Helen Braley-Mullen^*

From the Departments of Internal Medicine,^* Pathology, and Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia; and the Veterans Administration Research Service, Department of Veterans Affairs Medical Center, Columbia, Missouri

Granulomatous experimental autoimmune thyroiditis (G-EAT) isinduced by mouse thyroglobulin-sensitized splenocytes activatedin vitro with mouse thyroglobulin and interleukin (IL)-12. Thyroidlesions reach maximal severity 20 days after cell transfer,and inflammation either resolves or progresses to fibrosis byday 60 depending on the extent of thyroid damage at day 20.Depletion of CD8⁺ T cells inhibits G-EAT resolution. Our previousstudies indicated that IL-10 was generally higher in G-EAT thyroidsthat resolved. Using both wild-type and IL-10^–/–CBA/J mice, this study was undertaken to determine whether G-EATresolution would be inhibited in the absence of IL-10. The resultsshowed that either depletion of CD8⁺ T cells or IL-10 deficiencyincreased fibrosis and inhibited resolution of inflammation.We also found a correlation between higher expression levelsof proinflammatory cytokines and preferential expression levelsof proapoptotic molecules, such as FasL and TRAIL, and antiapoptoticmolecules, such as FLIP and Bcl-xL, in inflammatory cells fromthyroids of both CD8-depleted and IL-10-deficient mice. Furthermore,many of the CD8⁺ T cells were also IL-10⁺. These results suggestthat IL-10 plays an important role in G-EAT resolution and mightpromote resolution, at least in part, through its productionin CD8⁺ T cells. Further understanding of the mechanisms thatpromote the resolution of inflammation will facilitate the developmentof novel strategies for treating autoimmune diseases.