The Effect of Vitamin D Deficiency on Vitamin D Receptor Expression in a VDR/Cre Reporter Mouse and the Effect of Vitamin D on Survival and Natural Killer Cells in Influenza A Infection
Open Access
Author:
Johnston, Alexis
Graduate Program:
Pathobiology (MS)
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
November 04, 2022
Committee Members:
Margherita Teresa-Anna Cantorna, Thesis Advisor/Co-Advisor Vishal Singh, Committee Member Kumble Prabhu, Program Head/Chair Robert Paulson, Committee Member Troy Clavell Sutton, Committee Member
Keywords:
vitamin d natural killer cell nk cell influenza vdr cyp27b1
Abstract:
Many immune cells express the vitamin D receptor (VDR) at low levels in a resting state,
upregulating the receptor after activation. We previously reported characterization of a VDRtdTomato
reporter mouse which identifies cells that originate from a VDR-dependent lineage based on
expression of tdTomato as measured by flow cytometry. The majority of splenic immune cells are
tdTomato+ and thus originate from VDR-dependent lineages in D+ VDRtdTomato mice. Vitamin D
deficiency alters the frequency of tdTomato+ immune cells. Splenic monocytes, macrophages, T,
B, and NK cells significantly decrease in the frequency of tdTomato+ cells from D- VDRtdTomato
mice indicating a larger proportion of cells did not originate from VDR-dependent lineages and
have not expressed the VDR. tdTomato+ frequency in splenic neutrophils was not altered by
vitamin D deficiency.
NK cells have been shown to express the VDR and are tdTomato+ in D+ mice. The
function of the VDR in NK cells remains unclear. NK cells play a critical role in influenza A
infection, a common human pathogen. WT and CYP27B1-KO mice on D+ or D- diets were infected
with A/California/09/H1N1 influenza virus. CYP27B1-KO mice regardless of diet showed a
significant decrease in survival and greater symptom severity. D- CYP27B1-KO mice did not fully
resolve symptoms by d14 post-infection. No differences between groups were observed in splenic
NK cell frequencies, IFN-γ production, or maturation at d6 post-infection.
