Immunomodulatory Actions of Vitamin D Metabolites and their Potential Relevance to Human Lung Disease

The non-classical role for vitamin D in maintaining immune homeostasis has been recognised for 30 years. A definitive link between vitamin D status and the immune response has now been established by a multitude of association studies which link both vitamin D deficiency and genetic polymorphisms in vitamin D-related genes to susceptibility to respiratory diseases including tuberculosis, upper respiratory tract infection, chronic obstructive pulmonary disease (COPD), asthma and lung cancer. This review considers the mechanisms by which immune cells and lung epithelial cells respond to infection or injury by inducing intracellular metabolism of vitamin D. The effects of vitamin D metabolites on induction of phagocyte antimicrobial responses, modulation of DC maturation and T cell priming, skewing of the cytokine milieu towards a type 2 inflammatory response and promotion of regulatory T (Treg) cell development will also be described.