The cellular and molecular basis for the impact of vitamin A on immunity. (360G-Wellcome-091823_Z_10_Z)

While blindness is an apparent consequence of vitamin A deficiency, incapacitation of the immune system is another devastating result. The studies presented investigate the role of retinoic A (RA) on the development of immunity. We hypothesize that RA exerts a profound impact on the lineage commitment of mature leukocytes. At a systems level, we study its essential role in the development of acquired immunity, and in the complex diseases of cancer, graft rejection and autoimmunity. At a cellular level, responding leukocytes will be studied in vivo at the single cell level, permitting the visualization of antigen-specific immunity in RA-replete or deficient environments. Through the conditional ablation of RA signaling, the RA responsiveness of defined leukocyte subsets will be genetically controlled in vivo, allowing us to define strict cause and effect relationships between RA signaling, specific cell type and overall immunity. A picture of the temporal and spatial synthesis of RA and RA signaling will emerge using engineered reporting mice . Finally, the genetic and epigenetic basis for how RA programs leukocyte differentiation will be determined. These studies span from the fundamental molecular regulation of the immune system by RA to the translational use of regulatory T cells to treat disease.