Vitamin A deficiency impacts acquisition, but not expression, of autoimmunity to the neuroretina

Abstract

Purpose : Vitamin A (VitA) and its derivative retinoic acid are essential for immunological responses. Acquisition of effector responses is impeded in VitA deficient (VAD) mice. However, little is known about maintenance and expression of previously acquired effector function in the VAD environment or its impact on progression of autoimmune diseases. We examined this using experimental autoimmune uveitis (EAU) induced by immunization and spontaneous uveitis in IRBP TCR transgenic (R161H) mice.

Methods : VAD was induced by dietary lack of VitA from before birth or by daily injections of a pan-retinoic acid receptor inhibitor BMS493 in adult mice. EAU was induced by immunization with IRBP161-180 peptide. R161H mice develop uveitis spontaneously by 2–3 months of age. R161H T cells were activated in vitro in the presence of IRBP peptide for 3 days and adoptively transferred into control or VAD recipients. As an additional autoimmune model we used experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin basic protein and pertussis toxin.

Results : VAD mice were essentially resistant to EAU or EAE and displayed impaired effector T cell responses. Defective priming/acquisition of effector function by VAD T cells was also evident in vitro. Interestingly, effector T cells primed in a VitA-sufficient environment were able to function in VAD recipients, as evidenced by maintenance of high lineage-specific effector cytokine production and induction of EAU. Furthermore, R161H mice fed with VAD diet, in which the priming of pathogenic T cells had occurred before onset of VAD, developed exacerbated spontaneous uveitis compared to VitA-sufficient R161H mice.

Conclusions : We conclude that although priming of naïve T cells in the VAD environment is defective, effector function acquired under VAD sufficient conditions is maintained and can be expressed under VAD conditions. Our findings may shed light on immunity and autoimmunity in geographical regions where dietary VitA is limiting.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.