Colitis in a transgenic mouse model of autoimmune uveitis may be induced by neoantigen presentation in the bowel

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.

Whey Protein Hydrolysate Exerts Anti-Inflammatory Effects to Alleviate Dextran Sodium Sulfate (DSS)-Induced Colitis via Microbiome Restoration

“…In addition, we identified the most prominent biochemical metabolic and signaling pathways involved in differential proteins by KEGG pathway analysis. The results showed (Figure 6D) that the DEPs in the WPH-H/Model were mainly enriched in the antigen processing and presentation pathway, which is thought to be a possible critical pathway for the induction of colitis [44]. And the differentially expressed proteins induced by WPH intervention were mainly concentrated in the MHC class I pathway of the antigen processing and presentation pathway.…”