Developmental Vitamin D Deficiency and the Vitamin D Receptor Control Hematopoiesis

Area of Science:

• Immunology
• Endocrinology
• Developmental Biology

Background:

• Vitamin D status, the vitamin D receptor (VDR), and active vitamin D production are crucial for fetal and adult hematopoiesis.
• Understanding VDR expression in immune cells is key to deciphering vitamin D's role in immunity.
• Maternal vitamin D deficiency can impact offspring's immune development and function.

Purpose of the Study:

• To investigate the role of vitamin D and VDR in fetal and postnatal immune cell development.
• To determine the impact of maternal vitamin D deficiency on immune cell VDR expression and immune response to viral infection.
• To assess the therapeutic potential of vitamin D supplementation in mitigating these effects.

Main Methods:

• Utilized transgenic reporter mice (Vdr/tdTomato) to track VDR expression in hematopoietic cells.
• Induced maternal vitamin D deficiency (D-) or used VDR/Cyp27b1 knockout models.
• Assessed fetal progenitor populations, adult immune cell frequencies, VDR expression, and susceptibility to H1N1 influenza infection.
• Administered vitamin D supplementation to deficient mice.

Main Results:

• VDR expression was detected in hematopoietic progenitors as early as embryonic day 15.5.
• Maternal vitamin D deficiency led to reduced fetal progenitors and decreased VDR expression in adult immune cells (T cells, ILCs).
• Offspring from vitamin D-deficient mothers showed increased susceptibility to H1N1 influenza infection.
• Vitamin D supplementation restored VDR expression and partially improved resistance to H1N1 infection.

Conclusions:

• Vitamin D and VDR regulate hematopoiesis during both fetal and postnatal development.
• Developmental vitamin D deficiency has lasting effects on adult immune VDR expression and impairs antiviral responses.
• Vitamin D supplementation can partially reverse these deficits, highlighting its importance for robust immune function.