Vitamin D and 1,25(OH)2D Regulation of T Cells

Authors and Affiliations

• Margherita T. Cantorna
• Lindsay Snyder
• Yang-Ding Lin
• Linlin Yang
• Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University

Abstract

• Vitamin D regulates T cells directly and indirectly.
• 1,25 dihydroxyvitamin D (1,25(OH)2D) affects human invariant natural killer (iNK)T cells.
• In vivo effects of Vitamin D:
  • Inhibits T cell proliferation.
  • Inhibits IFN-γ and IL-17.
  • Induces IL-4 and T regulatory cells.
  • Requires NKT cells, IL-10, IL-10R, and IL-4 for effectiveness.

Introduction

• Vitamin D is either ingested or synthesized in the skin.
• Inactive form is converted to active 1,25(OH)2D in the liver and kidney.
• Regulates calcium, bone metabolism, cell growth, and immune system.
• VDRs (Vitamin D Receptors) found in immune system cells, including T cells.

T Cells and Immune Response

• T cells defend against various insults:
  • CD4+ T cells assist B cells and other cells.
  • Th1 cells control intracellular infections (e.g., Mycobacterium tuberculosis).
  • Th2 cells defend against parasites.
  • Th17 cells resist extracellular pathogens.
  • NKT cells recognize lipid antigens.
• Dysregulated T cells can cause immune-mediated diseases.

Vitamin D and T Cells

• Vitamin D inhibits T cell proliferation and cytokine secretion.
• Direct effects include inhibition of IL-2, IFN-γ, and IL-17 transcription.
• Induces IL-10 and T regulatory cells development.
• Modulates T cell localization and proliferation.
• Affects CD8+ T cells and iNKT cells:
  • Inhibits CD8 T cell proliferation.
  • Modifies cytotoxic T cell function.
• Experimental treatments show Vitamin D suppresses Th1/Th17-mediated diseases (e.g., EAE, IBD, diabetes).

Vitamin D Regulation of Mouse vs. Human T Cells

• Most studies conducted in mice; human studies less replicable.
• VDR expression is induced post T cell activation (48-72h).
• 1,25(OH)2D inhibits human and mouse T cell proliferation, similar effects observed between species.

Conclusions

• Vitamin D targets T cells, inhibiting proliferation and cytokine production.
• Regulates immune responses, potentially limiting immune-mediated diseases.
• Effects of Vitamin D require prolonged activation period (48-72h).

Acknowledgements

• Supported by National Institutes of Neurologic and Stroke Grant, National Center for Complementary and Alternative Medicine, and Office of Dietary Supplements.

References

• Various studies on Vitamin D metabolism, immune function, and effects on T cell responses.

These notes cover the key points from the document on the regulation of T cells by Vitamin D and its derivatives, emphasizing the physiological roles of Vitamin D in immune modulation and disease prevention.