DAPT reverses the Th17/Treg imbalance in experimental autoimmune uveitis in vitro via inhibiting Notch signaling pathway.

Uveitis is the most common cause in inflammatory eye diseases that can lead to visual impairment even blindness worldwide. T helper (Th) 17 and regulatory T (Treg) cells are critical mediators for immune response. Notch signaling can regulate the cell differentiation, playing a role in the pathogenesis of the diseases. In this study, we measured the expression levels of Notch1, DLL4, IL-10, IL-17, RORγt and Foxp3 in T cells from lymph node, spleen and eye tissues in experimental autoimmune uveitis (EAU) rats in vitro, determined the ratios of CD4+/CD8+ and Th17/Treg. Moreover, we also investigated the effect of Notch signaling inhibitor N-(N-(3,5-Difluorophenacetyl-L-alanyl))-S-phenylglycine t-Butyl Ester (DAPT) on Notch1, DLL4 expression and on Th17, Treg cell differentiation. The results indicated that the pathogenesis of uveitis accompanied by the elevated expression of Notch1, DLL4, IL-10, IL-17, RORγt, and Foxp3 as well as the imbalanced CD4+/CD8+ and Th17/Treg ratios. By contrast, inhibition of Notch signaling by DAPT can efficiently decrease Th17 cell response, downregulate the expression of Notch1, DLL4, IL-17 and the transcription of RORγt, reduce Th17 levels and restore the CD4+/CD8+, Th17/Treg balance. Moreover, DAPT can also inhibit Th17 cell differentiation in healthy rats, though the inhibitory capacity of Th17, Treg differentiation is less than that in EAU rats. Overall, Notch signaling activation can lead to the disturbed Th17/Treg balance in uveitis, whereas inhibition of Notch signaling can ameliorate the inflammatory response and may be a potential immunoregulatory strategy in patients with uveitis.

Uveitis in celiac disease with an excellent response to gluten-free diet: third case described.

To describe the case of a patient with celiac disease who achieved a complete response to a gluten-free diet. A 28-year-old woman presented with diarrhea, oral ulcers, and refractory uveitis of 2.5-years duration. She was treated with prednisone, mydriatic drops, and infliximab with no response. She was referred to our hospital at which point her previous diagnosis of uveitis was confirmed; she was also diagnosed with right-sided sacro-iliitis. The patient did not have arthritis or any skin conditions. Three tests for fecal parasites and a fecal leukocyte were negative. Endoscopy revealed atrophic appearance of the duodenal mucosa. Biopsy showed atrophy of the duodenal villi with intra-epithelial lymphocytes, hyperplasia of the crypts, and chronic inflammatory infiltrate. The search for antiendomysial antibody was >1/1,280. The patient was started on a gluten-free diet and after 3 months demonstrated significant improvement of gastrointestinal symptoms and uveitis, as well as a reduction of antiendomysial antibodies (1/80). After 6 months, there was complete remission of gastrointestinal symptoms and total control of uveitis. The antiendomysial antibody was negative at that time. Clinical uveitis as a manifestation of celiac disease has been described in only two cases in the literature. This case study is the third to demonstrate that uveitis is a clinical symptom that can be addressed in patients with celiac disease.

Uveitis responding on gluten free diet in a girl with celiac disease and diabetes mellitus type 1.

A 9-year old girl with a history of diabetes mellitus type 1, presented with visual loss of the left eye. The right eye examination was unremarkable. Slit-lamp examination revealed few small and fine keratic precipitates. We noted 2+ flare in the vitreous. There was no choroiditis, papillitis or retinal vasculitis. No aetiology was found. The patient was treated by topical and systemic corticosteroids without any improvement. Celiac disease was discovered by the presence of celiac antibodies in the work-up of joint pain and diabetes mellitus type 1. Antiendomysium antibodies and anti-transglutaminase antibodies were both positive. A small bowel biopsy confirmed celiac disease. A gluten free diet was set up and corticosteroids were tapered off. Recovery of the uveitis was obvious during gluten free diet and normalized within two months.