Extrinsic Regulation of Hematopoietic Stem Cells and Lymphocytes by Vitamin A

Abstract

Vitamin A and its receptors, retinoic acid receptors (RARs), are key regulators of hematopoiesis. This review focuses on the extrinsic regulation of hematopoiesis by retinoids, predominantly focusing on studies in mice, but also highlighting some of the studies performed using human hematopoietic stem cells (HSCs). RARγ has key roles in regulating B and T lymphocytes via distinct bone marrow mesenchymal cells and thymic microenvironment cells, respectively. The hematopoietic phenotypes caused by vitamin A deficiency are largely due to microenvironment-induced phenotypes that occur due to RARγ deficiency. Studies using human HSCs have also revealed that the biologically active form of vitamin A increases the HSC-support potential of immature mesenchymal cell lines. Distinct roles have been revealed for different vitamin A receptors in regulating hematopoiesis. Further elucidation of the mechanisms whereby the RARs extrinsically regulate immune cells and HSCs may provide insights leading to the development of improved therapeutics to manipulate the numbers of these cells in normal and diseased states.