Role of vitamin D in cytotoxic T lymphocyte immunity to pathogens and cancer

Abstract

The discovery of vitamin D receptor (VDR) expression in immune cells has opened up a new area of research into immunoregulation by vitamin D, a niche that is distinct from its classical role in skeletal health. Today, about three decades since this discovery, numerous cellular and molecular targets of vitamin D in the immune system have been delineated. Moreover, strong clinical associations between vitamin D status and the incidence/severity of many immune-regulated disorders (e.g. infectious diseases, cancers and autoimmunity) have prompted the idea of using vitamin D supplementation to manipulate disease outcome. While much is known about the effects of vitamin D on innate immune responses and helper T (T_H) cell immunity, there has been relatively limited progress on the frontier of cytotoxic T lymphocyte (CTL) immunity – an arm of host cellular adaptive immunity that is crucial for the control of such intracellular pathogens as human immunodeficiency virus (HIV), tuberculosis (TB), malaria, and hepatitis C virus (HCV). In this review, we discuss the strong historical and clinical link between vitamin D and infectious diseases that involves cytotoxic T lymphocyte (CTL) immunity, present our current understanding as well as critical knowledge gaps in the realm of vitamin D regulation of host CTL responses, and highlight potential regulatory connections between vitamin D and effector and memory CD8 T cell differentiation events during infections.

• Calcitriol
• CD8 T cells
• Cyp27B1
• differentiation
• effector cells
• immunological memory
• protective immunity
• vitamin D receptor

Acknowledgements

The authors would like to thank graduate students, Mr. Yevgeniy Yuzefpolskiy and Mr. Florian Martin Baumann, for helpful discussions and for critically proofreading the manuscript. We would acknowledge the contributions of other studies in the field of vitamin D and immune regulation that could not all be referenced in this review because of space constraint.

Declaration of interest

This work was funded through a Research Scholar Grant titled “Regulation of Protective T Cell Immunity by Vitamin D” from The American Cancer Society (127435-RSG-15-014-01-CNE) and Seed Funds from Seattle Children's Research Institute, Seattle, WA. The authors declare no conflicts of interests.