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E. C. Kerr, D. A. Copland, A. D. Dick, L. B. Nicholson; IL-17 Producing Cells in the Eyes of Mice With Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2628.
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To investigate the involvement of Th17 cells in ocular autoimmune disease. Experimental autoimmune uveoretinitis (EAU) serves as an animal model for human inflammatory eye disease. It is a CD4+ T cell-mediated autoimmune disease and is thought of as a Th1 disorder. However, disease is exacerbated in the absence of either of the Th1 cytokines IFNγ or IL-12, and ameliorated by treatment with IFNγ. One explanation for this is a reciprocal relationship between pathogenic IL-17 producing CD4+ cells (Th17) and cells that produce IFNγ (which negatively regulate Th17 differentiation). In other models Th17 cells play a key role in pathology, but their relevance to EAU has not yet been established.
EAU was induced in mice by immunisation with a dominant ocular antigen in an adjuvant, and retinas, draining lymph nodes (dLNs) and spleens were excised at peak disease. Single cell suspensions were generated from each tissue and infiltrating T cells were examined by flow cytometry for intracellular production of IFNγ and IL-17.
Both IFNγ-producing and IL-17-producing CD4+ cells were detected in the retina, dLNs and spleen. The proportion of CD4+ cells that produce IL-17 in the eye was found to be greater than that found in the spleen.
We have demonstrated that the production of IL-17 is associated with autoimmune infiltration in EAU. Differentiation of Th17 cells requires the combined presence of TGFß and IL-6. TGFß is constitutively expressed in the eye and IL-6 is produced in the eye during EAU as part of the inflammatory response. This raises the possibility that these cytokines could promote Th17 differentiation within the target organ.
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