Vitamin D deficiency is highly prevalent in pregnant women (> 80%) and children (>75%). Beneficial effects of vitamin D on atopic allergic responses have been suggested to be mediated through Regulatory T cell population (Treg cells). Treg cell function are implicated in Non communicable diseases as well. Treg cells are known to play a significant role in the maintenance of maternal tolerance to the fetus and are detected in the human decidua and peripheral blood throughout pregnancy. Treg cell population, that comprises less than 1 % of peripheral CD4+ cells, has the ability to suppress both Th1 and Th2 immunity against paternal/ fetal alloantigen, a process, critical for immune regulation and continuation of pregnancy
Vitamin D deficiency and Regulatory T cells in pregnant women
1. Dr. R. Hemalatha
Scientist’F & HOD
Clinical Division
National Institute of Nutrition (ICMR, DHR)
India
Vitamin D deficiency and Regulatory T cells in
pregnant women
Dr. R. Hemalatha and Vijayendra Chary A, J Steroid Biochem Mol Biol. 2015
Mar;147:48-55. doi: 10.1016/j.jsbmb.2014.11.020.
2. Vitamin D deficiency is highly prevalent in women (>80 %) and children (>75%) in
India
Vitamin D deficiency during pregnancy has been linked with complications such as
preeclampsia, insulin resistance, gestational diabetes and atopic allergic reactions in
infants.
Beneficial effects of vitamin D on atopic allergic responses have been suggested to
be mediated through Regulatory T cell population (Treg cells). Treg cell function
are implicated in Non communicable diseases as well
Treg cell population, that comprises less than 1 % of peripheral CD4+ cells, has the
ability to suppress both Th1 and Th2 immunity against paternal/ fetal alloantigen, a
process, critical for immune regulation and continuation of pregnancy
Regulatory T cells (CD4+/CD25+/CD127-/FOXP3 or Treg cells) are subsets of T
lymphocytes described by expression of a specific transcription factor, Forkhead box
P3 (FOXP3). Treg cells are reduced in both human and mouse during allergic
conditions
3. UVB
290-315
Epidermis
7- Dehydrocholesterol
Vitamin D3
or
Cholecalciferol
VDBP
Liver
25 (OH)D3
Intestine
Kidney
1, 25 (OH)2 D3
25
(OH)D3
VDBP
Bone
Bone densitometry &
Ca+ & Po4- absorption
Osteoporotic fracture
Immune system
Treg cells
Phagocytic function
Pro inflammatory
Cytokines, CRP
Pancreas
Insulin secretion
Type I DM incidence
Insulin resistance
Intestine
Ca+ & Po4- absorption
Pregnancy
Risk of SGA
Risk of GDM
immunity?
Vitamin D source
from sun light
> 90%
Vitamin D from
food source
<10%
4. Vitamin D is activated by two enzymatic steps
Vitamin D3 (cholecalciferol) is metabolized to 25-hydroxycholecalciferol (calcidiol or 25-
hydroxyvitamin D3 or 25(OH)D3) by the hepatic 25-hydroxylases (CYP2R1) in the liver
Subsequently, 25(OH)D3 is converted to 1, 25-dihydroxycholecaciferol (calcitriol or
1,25(OH)2D3) by 1α-hydroxylase (CYP27B1) in the kidney.
The active form of vitamin D3 (calcitriol) complexes with vitamin D receptor (VDR) and
forms a heterodimer with 9-cis-retinoic acid receptor (RXR) and interacts with specific DNA
sequences of target genes
Calcitriol formation takes place in several other cell types, including dermal, intestinal
epithelial cells, lymph nodes, monocytes and placenta, express CYP27B1 enzyme, that
enables extra renal activation of 25(OH)D3 to the active hormonal form1,25(OH)2D3
Vitamin D metabolising enzymes (CYP2R1, CYP27B1, CYP24A1) expressions were
altered, suggesting altered vitamin D homeostasis in pregnant women with vitamin D
deficiency, which is likely to play an important role in the foetal immune development and
overall foetal development as well.
R Hemalatha .etal J Steroid Biochem Mol Biol. 2015
Mar;147:48-55. doi: 10.1016/j.jsbmb.2014.11.020.
5. R Hemalatha .etal J Steroid Biochem Mol Biol. 2015
Mar;147:48-55. doi: 10.1016/j.jsbmb.2014.11.020.
Maternal 25(OH)D3 was significantly higher than
cord blood and was directly correlated with cord
blood vitamin D
Treg cell population increases right from the very
early stages of pregnancy
Treg cell population were significantly lower in
vitamin D deficient mothers
The FOXP3 (Treg cell trnascription factor) mRNA
expression in the placenta tissues was
downregulated in 25(OH)D3 deficient pregnant
In addition, regulatory cytokines, IL-10 and TGF β
were decreased in vitamin D deficient subjects
Women with impaired Treg cell concentration
suffer from spontaneous abortion and infertility
6. Vitamin D plays an important role in the maintenance of
B cell homeostasis and B cell-mediated autoimmune
disorders
The vitamin D regulates IgE levels in the serum via a
direct effect on the VDR expression on B cells
CD23 and CD21 are substrates on the B lymphocytes
that act as receptors for IgE antibody and are linked to
asthma/ allergy in children as well as in adults.
The expression of CD23 and CD21 on B cells has been
shown to have an important role in IgE production
during fetal development
Vitamin D deficient pregnant women had high IgE
receptors (CD23 and CD21) expression in B cells and
placenta tissue
CD23 and CD21 on B cells are linked with increased
respiratory morbidity amongst vitamin D deficient
subjects
R hemalatha et al . J Steroid Biochem Mol Biol. 2015, Mar;147:48-55. doi:
10.1016/j.jsbmb.2014.11.020.
7. Vitamin D deficiency in Pregnant women- Summary
Maternal vitamin D influences the spectrum of immune cells.
Regulatory T cell function (Treg cells) is affected by vitamin D status.
IgE receptors expression on B cells increases with vitamin D deficiency.
Vitamin D affects several vitamin D and immunity related genes in
placenta.
The results from the current study show that impaired maternal 25(OH)D3
during pregnancy influences the spectrum of immune cells such as
regulatory T cells and B cells with IgE receptors in the maternal and cord
blood, which in turn may be important in maintaining optimal fetal health
and pregnancy outcomes.
Dr. R. Hemalatha and Vijayendra Chary A, J Steroid Biochem Mol Biol. 2015
Mar;147:48-55. doi: 10.1016/j.jsbmb.2014.11.020.