May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
IL-17 Producing Cells in the Eyes of Mice With Experimental Autoimmune Uveoretinitis
Author Affiliations & Notes
  • E. C. Kerr
    University of Bristol, Bristol, United Kingdom
    Cellular and Molecular Medicine,
  • D. A. Copland
    University of Bristol, Bristol, United Kingdom
    Academic Unit of Ophthalmology, Clinical Sciences South Bristol,
  • A. D. Dick
    University of Bristol, Bristol, United Kingdom
    Academic Unit of Ophthalmology, Clinical Sciences South Bristol,
  • L. B. Nicholson
    University of Bristol, Bristol, United Kingdom
    Cellular and Molecular Medicine,
  • Footnotes
    Commercial Relationships E.C. Kerr, None; D.A. Copland, None; A.D. Dick, None; L.B. Nicholson, None.
  • Footnotes
    Support NERC
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2628. doi:
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    • Get Citation

      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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: 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.

Methods:: 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.

Results:: 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.

Conclusions:: 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.

Keywords: uveitis-clinical/animal model • retina • cytokines/chemokines 
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