Pharmacological doses of vitamin A deteriorate lupus-like disease in the MRL/lpr mouse model (THER5P.829)

The critical roles of retinoic acid (RA), a metabolite of vitamin A (VA), in both tolerogenic and immunogenic immune responses have been documented. However, how VA affects the development of autoimmunity is still unclear. Here we demonstrate that pharmacological doses of VA had adverse effects on the development of autoimmune lupus in the MRL/lpr mouse model. We administered, orally, RA (6 mg/kg body weight/day) or retinyl palmitate combined with 10% RA (VARA, a total of 6.6 mg/kg/day) to the mice starting from 6 weeks of age. At this age, the mice do not exhibit overt signs of lupus. However, the immunogenic environment preceding disease onset has been established that is evidenced by an increase of total IgM/IgG in the plasma and expansion of lymphocytes and dendritic cells in secondary lymphoid organs. After 8 weeks of RA or VARA treatment, significantly higher pathological scores in kidney, lung, and brain were observed, which were correlated with a marked increase in B-cell responses. In addition, although the number of T cells in the mesenteric lymph node decreased with RA that led to reduced tissue weight, the proportions of T-cell subsets did not change. Importantly, neither RA nor VARA affected regulatory T cells in these mice. Altogether, our results suggest that under the immunogenic environment in autoimmune lupus, VA can generate more severe disease rather than inducing tolerance. Thus, administration of VA in lupus treatment should be approached with caution.