Vitamin A Deficiency Deteriorates Lupus Nephritis.

Abstract

Abstract Vitamin A deficiency (VAD) is observed in both human and mice with lupus nephritis (LN). However, whether VAD is a driving factor for LN progression is unclear. Here, we investigated the effect of VAD on the progression of LN in a lupus-prone mouse model, MRL/lpr. In these mice, while LN is not apparent before 8 weeks of age, the inflammation of lymphoid tissues suggesting initiation of lupus is evident at weaning. Thus, we initiated VAD either before or after weaning to reveal a potential time-dependent effect. At around 15 weeks of age with both types of VAD, we found exacerbated LN that was characterized by deteriorated kidney inflammation, impaired renal epithelial integrity, and dramatic squamous metaplasia of the renal pelvic urothelium. Both types of VAD provoked severe neutrophilic tubulointerstitial nephritis and accelerated renal failure. This was concomitant with significantly higher mortality in all VAD mice. Looking at an earlier time point of 7 weeks of age and before the onset of clinical LN, both types of VAD increased splenomegaly, lymphadenopathy, and circulating autoantibodies; three additional hallmarks of lupus, as well as renal infiltration of conventional and plasmacytoid dendritic cells. These results suggest VAD-driven deterioration of LN regardless of the time of VAD initiation. Our findings raise significant public health concerns that concurrent lupus and VAD may lead to more severe SLE. Future studies will elucidate the underlying mechanisms of how VAD modulates myeloid cells to accelerate the initiation of LN.