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Abstract
Undifferentiated uveitis (intraocular inflammation, IOI) is an idiopathic sight-threatening, presumed autoimmune disease, accountable for ~ 10% of all blindness in the developed world. We have investigated the association of uveitis with inflammatory bowel disease (IBD) using a mouse model of spontaneous experimental autoimmune uveoretinitis (EAU). Mice expressing the transgene (Tg) hen egg lysozyme (HEL) in the retina crossed with 3A9 mice expressing a transgenic HEL-specific TCR spontaneously develop uveoretinitis at post-partum day (P)20/21. Double transgenic (dTg TCR/HEL) mice also spontaneously develop clinical signs of colitis at ~ P30 with diarrhoea, bowel shortening, oedema and lamina propria (LP) inflammatory cell infiltration. Single (s)Tg TCR (3A9) mice also show increased histological LP cell infiltration but no bowel shortening and diarrhoea. dTg TCR/HEL mice are profoundly lymphopenic at weaning. In addition, dTg TCR/HEL mice contain myeloid cells which express MHC Class II-HEL peptide complexes (MHCII-HEL), not only in the inflamed retina but also in the colon and have the potential for antigen presentation. In this model the lymphopenia and reduction in the absolute Treg numbers in dTg TCR/HEL mice is sufficient to initiate eye disease. We suggest that cell-associated antigen released from the inflamed eye can activate colonic HEL-specific T cells which, in a microbial micro-environment, not only cause colitis but feedback to amplify IOI.
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1 University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, UK (GRID:grid.7107.1) (ISNI:0000 0004 1936 7291); Medical University of Vienna, Vienna General Hospital, Department of General Surgery, Division of Visceral Surgery, Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492)
2 University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, UK (GRID:grid.7107.1) (ISNI:0000 0004 1936 7291); University of Glasgow, Wolfson Wohl Cancer Research Centre, Flow Facility, Bearsden, UK (GRID:grid.8756.c) (ISNI:0000 0001 2193 314X)
3 University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, UK (GRID:grid.7107.1) (ISNI:0000 0004 1936 7291)
4 University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, UK (GRID:grid.7107.1) (ISNI:0000 0004 1936 7291); Guy’s Hospital, Centre for Gene Therapy and Regenerative Medicine, London, UK (GRID:grid.239826.4) (ISNI:0000 0004 0391 895X)
5 University of Oxford, Nuffield Department of Medicine, Henry Wellcome Building for Molecular Physiology, Headington, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948)
6 University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, UK (GRID:grid.7107.1) (ISNI:0000 0004 1936 7291); Aberdeen Royal Infirmary, NHS Grampian, Eye Clinic, Aberdeen, UK (GRID:grid.417581.e) (ISNI:0000 0000 8678 4766)