Interleukin-10 promotes resolution of granulomatous experimental autoimmune thyroiditis.
Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by mouse thyroglobulin-sensitized splenocytes activated in vitro with mouse thyroglobulin and interleukin (IL)-12. Thyroid lesions reach maximal severity 20 days after cell transfer, and inflammation either resolves or progresses to fibrosis by day 60 depending on the extent of thyroid damage at day 20. Depletion of CD8(+) T cells inhibits G-EAT resolution. Our previous studies indicated that IL-10 was generally higher in G-EAT thyroids that resolved. Using both wild-type and IL-10(-/-) CBA/J mice, this study was undertaken to determine whether G-EAT resolution would be inhibited in the absence of IL-10. The results showed that either depletion of CD8(+) T cells or IL-10 deficiency increased fibrosis and inhibited resolution of inflammation. We also found a correlation between higher expression levels of proinflammatory cytokines and preferential expression levels of proapoptotic molecules, such as FasL and TRAIL, and antiapoptotic molecules, such as FLIP and Bcl-xL, in inflammatory cells from thyroids of both CD8-depleted and IL-10-deficient mice. Furthermore, many of the CD8(+) T cells were also IL-10(+). These results suggest that IL-10 plays an important role in G-EAT resolution and might promote resolution, at least in part, through its production in CD8(+) T cells. Further understanding of the mechanisms that promote the resolution of inflammation will facilitate the development of novel strategies for treating autoimmune diseases.
Fang
Yujiang
Y
Department of Internal Medicine, University of Missouri, Columbia, MO 65212, USA.
Sharp
Gordon C
GC
Braley-Mullen
Helen
H
D000818:Animals; D017209:Apoptosis; D016827:CD8 Antigens / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005355:Fibrosis; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology* / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology; D013968:Thyroiditis, Subacute / Q000276:immunology* / Q000473:pathology
D016827:CD8 Antigens; D016207:Cytokines; D016753:Interleukin-10; D013954:Thyroglobulin